SNPMiner Trials by Shray Alag

NCT00511368 (37) NCT00460382 (36) NCT04504071 (35) NCT03783286 (33) NCT04172597 (32) NCT02404233 (29) NCT00959894 (28) NCT00706147 (28) NCT00121017 (28) NCT01685801 (27) NCT04513626 (26) NCT01736761 (26) NCT04495348 (24) NCT02673398 (23) NCT02499978 (22) NCT01605084 (21) NCT04254705 (21) NCT02069834 (21) NCT00939770 (18) NCT01792570 (18) NCT01199939 (18) NCT00356616 (18) NCT02728258 (17) NCT02707601 (17) NCT02770508 (16) NCT00711009 (16) NCT00630864 (16) NCT00491556 (15) NCT04085315 (15) NCT02616029 (15) NCT00830804 (15) NCT01170962 (14) NCT00984152 (14) NCT03953898 (14) NCT00727597 (14) NCT03212274 (14) NCT00337467 (13) NCT00098293 (13) NCT02159599 (13) NCT00424814 (12) NCT04432454 (12) NCT02527096 (12) NCT01849003 (12) NCT03781063 (12) NCT03683524 (11) NCT01614457 (11) NCT00460746 (11) NCT00993148 (11) NCT03061331 (11) NCT02494882 (11) NCT03068312 (11) NCT04453436 (11) NCT01521338 (10) NCT01614470 (10) NCT01423812 (10) NCT00358917 (10) NCT04415268 (10) NCT00511381 (10) NCT03911713 (9) NCT02742519 (9) NCT02725567 (9) NCT03045523 (9) NCT00438152 (9) NCT01102972 (9) NCT02971839 (9) NCT00740064 (9) NCT02605954 (9) NCT00379405 (9) NCT01562847 (9) NCT02616783 (9) NCT04272242 (9) NCT02445053 (9) NCT00242840 (9) NCT02724527 (9) NCT04209465 (9) NCT04585737 (8) NCT02082977 (8) NCT00112775 (8) NCT00383318 (8) NCT03659214 (8) NCT03631732 (8) NCT00118898 (8) NCT01888562 (8) NCT02633189 (8) NCT03565692 (8) NCT03843775 (8) NCT01161576 (8) NCT02167165 (8) NCT00344461 (8) NCT04519398 (7) NCT02154490 (7) NCT03232892 (7) NCT00650832 (7) NCT04549025 (7) NCT00440947 (7) NCT02784639 (7) NCT03572140 (6) NCT01237444 (6) NCT00532168 (6) NCT01102569 (6) NCT04424368 (6) NCT01414985 (6) NCT00525733 (6) NCT02308332 (6) NCT01487265 (6) NCT00049933 (5) NCT02389920 (5) NCT03351699 (5) NCT04197934 (5) NCT02272998 (5) NCT00122590 (5) NCT04204330 (5) NCT02450591 (5) NCT01173029 (5) NCT02675829 (5) NCT02858921 (5) NCT01914484 (5) NCT00187733 (5) NCT02554591 (5) NCT01501604 (5) NCT02716116 (5) NCT01136460 (5) NCT00187655 (5) NCT00350272 (5) NCT00837135 (5) NCT03202862 (5) NCT01707199 (5) NCT03839342 (5) NCT01323010 (4) NCT02248324 (4) NCT01698905 (4) NCT01737359 (4) NCT01306045 (4) NCT02804100 (4) NCT01456676 (4) NCT00588172 (4) NCT03434418 (4) NCT03593993 (4) NCT01804140 (4) NCT02882308 (4) NCT03497767 (4) NCT04106024 (4) NCT02716311 (4) NCT04405674 (4) NCT03599518 (4) NCT01675778 (4) NCT01604122 (4) NCT01297777 (4) NCT04519970 (4) NCT00705679 (4) NCT04147351 (4) NCT04129502 (4) NCT03976856 (4) NCT02335944 (4) NCT03948763 (4) NCT03255083 (4) NCT04002830 (4) NCT02635815 (4) NCT03066206 (4) NCT01331642 (4) NCT00557245 (4) NCT01922583 (4) NCT02893332 (4) NCT03592888 (4) NCT02257424 (4) NCT03874858 (4) NCT00017732 (4) NCT00187720 (4) NCT02593539 (4) NCT01185587 (4) NCT04439292 (4) NCT03884348 (4) NCT01309243 (4) NCT03209063 (4) NCT04160546 (4) NCT03292302 (4) NCT02418234 (4) NCT02535338 (3) NCT02192697 (3) NCT03410043 (3) NCT03845296 (3) NCT02914990 (3) NCT02113813 (3) NCT01532011 (3) NCT04340388 (3) NCT00962533 (3) NCT03856411 (3) NCT04049266 (3) NCT02973763 (3) NCT02926092 (3) NCT00271973 (3) NCT04256941 (3) NCT03812809 (3) NCT02954523 (3) NCT01784068 (3) NCT03446417 (3) NCT02841579 (3) NCT02025114 (3) NCT01288521 (3) NCT01385683 (3) NCT02279004 (3) NCT00998582 (3) NCT03111901 (3) NCT01352715 (3) NCT01619774 (3) NCT01045369 (3) NCT02246998 (3) NCT03969823 (3) NCT00895596 (3) NCT02398929 (3) NCT00724711 (3) NCT04029350 (3) NCT03737994 (3) NCT01443806 (3) NCT02629822 (3) NCT03463525 (3) NCT00710112 (3) NCT03623750 (3) NCT04283955 (3) NCT02743923 (3) NCT01016106 (3) NCT01259089 (3) NCT03971474 (3) NCT02917993 (3) NCT02368990 (3) NCT00279110 (3) NCT02485652 (3) NCT00312169 (3) NCT04541407 (3) NCT02769286 (3) NCT00747487 (3) NCT04267913 (3) NCT01429597 (3) NCT04023617 (3) NCT03790228 (3) NCT01759888 (3) NCT04429152 (3) NCT01810718 (3) NCT02725632 (3) NCT01090011 (3) NCT04544111 (3) NCT02926768 (3) NCT02981108 (3) NCT02459743 (3) NCT00654823 (3) NCT01037127 (3) NCT04439305 (3) NCT01028222 (3) NCT01542411 (3) NCT01031446 (3) NCT02726269 (3) NCT01892644 (3) NCT03260491 (3) NCT01802632 (3) NCT02720094 (3) NCT02630186 (3) NCT01627132 (3) NCT02690675 (3) NCT01013506 (3) NCT04252339 (3) NCT02496663 (3) NCT03386955 (3) NCT03394118 (3) NCT04212702 (3) NCT01754025 (3) NCT01160276 (3) NCT00121979 (3) NCT03228277 (3) NCT04351555 (3) NCT01243346 (3) NCT04510415 (3) NCT02796274 (3) NCT02774005 (3) NCT02064491 (3) NCT04233021 (3) NCT03799601 (3) NCT00260260 (3) NCT02094261 (3) NCT04245085 (3) NCT01282151 (3) NCT03058094 (3) NCT02520778 (3) NCT03161808 (3) NCT04181060 (3) NCT01342679 (3) NCT01443273 (3) NCT01593254 (3) NCT04433481 (3) NCT02529995 (3) NCT03502850 (3) NCT02771314 (3) NCT03823807 (3) NCT03270527 (3) NCT02688881 (3) NCT01005602 (3) NCT02442349 (3) NCT02282267 (2) NCT02684591 (2) NCT03381430 (2) NCT02178397 (2) NCT03608215 (2) NCT02603107 (2) NCT03370770 (2) NCT03322696 (2) NCT00525473 (2) NCT03333343 (2) NCT03127449 (2) NCT01781026 (2) NCT02503722 (2) NCT00975871 (2) NCT03964233 (2) NCT03388099 (2) NCT02317016 (2) NCT03845270 (2) NCT03519958 (2) NCT03918304 (2) NCT02151721 (2) NCT02777658 (2) NCT01016444 (2) NCT02971501 (2) NCT03101254 (2) NCT03178617 (2) NCT01774721 (2) NCT03574753 (2) NCT01357655 (2) NCT01766713 (2) NCT02097225 (2) NCT00658164 (2) NCT03622593 (2) NCT02571036 (2) NCT00834665 (2) NCT00969137 (2) NCT02026011 (2) NCT03622580 (2) NCT03543683 (2) NCT01143493 (2) NCT03671538 (2) NCT04028778 (2) NCT00324961 (2) NCT01915576 (2) NCT02157883 (2) NCT01387022 (2) NCT03864042 (2) NCT03235245 (2) NCT03469960 (2) NCT02795884 (2) NCT00005541 (2) NCT01242813 (2) NCT02906020 (2) NCT03960645 (2) NCT00643058 (2) NCT03443336 (2) NCT02992860 (2) NCT02281760 (2) NCT02201602 (2) NCT04310007 (2) NCT03720665 (2) NCT04309019 (2) NCT00909532 (2) NCT00411944 (2) NCT01604681 (2) NCT01245062 (2) NCT00270231 (2) NCT03256136 (2) NCT03973918 (2) NCT00302692 (2) NCT00125281 (2) NCT02163733 (2) NCT02110407 (2) NCT00475176 (2) NCT03196882 (2) NCT01572818 (2) NCT02556333 (2) NCT04268550 (2) NCT02433717 (2) NCT03428126 (2) NCT01153763 (2) NCT02609776 (2) NCT01420211 (2) NCT03556176 (2) NCT03872440 (2) NCT01405079 (2) NCT03382795 (2) NCT02991950 (2) NCT00013598 (2) NCT03455764 (2) NCT02422628 (2) NCT03831932 (2) NCT03766490 (2) NCT02580474 (2) NCT00499577 (2) NCT02444884 (2) NCT01775943 (2) NCT03544814 (2) NCT01310036 (2) NCT01027663 (2) NCT01928160 (2) NCT01244438 (2) NCT00007150 (2) NCT04462081 (2) NCT02297425 (2) NCT02086071 (2) NCT01050400 (2) NCT03060590 (2) NCT01819428 (2) NCT02709668 (2) NCT02411448 (2) NCT03878719 (2) NCT04479306 (2) NCT03377023 (2) NCT01378026 (2) NCT00226551 (2) NCT03239145 (2) NCT04511533 (2) NCT02191891 (2) NCT04586270 (2) NCT04545710 (2) NCT02120222 (2) NCT02738593 (2) NCT00831272 (2) NCT04469543 (2) NCT00573495 (2) NCT04158544 (2) NCT00904150 (2) NCT02110056 (2) NCT02856893 (2) NCT02110043 (2) NCT02182986 (2) NCT04179890 (2) NCT00063232 (2) NCT02197234 (2) NCT03121235 (2) NCT01532089 (2) NCT03887169 (2) NCT02268864 (2) NCT01963845 (2) NCT00866736 (2) NCT03977194 (2) NCT03991013 (2) NCT02500927 (2) NCT02228382 (2) NCT02689570 (2) NCT01513785 (2) NCT02463435 (2) NCT03351361 (2) NCT04527549 (2) NCT03424759 (2) NCT02197247 (2) NCT02321046 (2) NCT04272034 (2) NCT04027647 (2) NCT02364609 (2) NCT02759835 (2) NCT04349865 (2) NCT00068159 (2) NCT00418015 (2) NCT04310397 (2) NCT03088176 (2) NCT03867175 (2) NCT00339209 (2) NCT00011258 (2) NCT01288430 (2) NCT01616199 (2) NCT03603262 (2) NCT03071705 (2) NCT00969930 (2) NCT00772408 (2) NCT02743468 (2) NCT00277342 (2) NCT04248829 (2) NCT01767454 (2) NCT00933127 (2) NCT03317873 (2) NCT03392246 (2) NCT01909453 (2) NCT03523104 (2) NCT00085917 (2) NCT02507921 (2) NCT03781752 (2) NCT03828422 (2) NCT02193282 (2) NCT03195452 (2) NCT02294487 (2) NCT01325441 (2) NCT02511106 (2) NCT02997501 (2) NCT04184921 (2) NCT00625092 (2) NCT01657786 (2) NCT01415011 (2) NCT02629523 (2) NCT01718847 (2) NCT02818023 (2) NCT00577707 (2) NCT01943422 (2) NCT00116636 (2) NCT01841463 (2) NCT04429542 (2) NCT03865511 (2) NCT01218477 (2) NCT03205267 (2) NCT02881320 (2) NCT01897480 (2) NCT02810990 (2) NCT04189757 (2) NCT01951001 (2) NCT04254939 (2) NCT03207867 (2) NCT00780949 (2) NCT03355768 (2) NCT00817089 (2) NCT02143466 (2) NCT04499053 (2) NCT01907776 (2) NCT00909727 (2) NCT01562028 (2) NCT03737253 (2) NCT00441974 (2) NCT02155465 (2) NCT04586335 (2) NCT00661999 (2) NCT02705339 (2) NCT04006340 (2) NCT04553887 (2) NCT03852290 (2) NCT02183922 (2) NCT03970239 (2) NCT00294372 (2) NCT03250676 (2) NCT03792074 (2) NCT00671892 (2) NCT00689182 (2) NCT00106379 (2) NCT01947023 (2) NCT00509652 (2) NCT03683251 (2) NCT02039986 (2) NCT03515837 (2) NCT04081688 (2) NCT03190005 (2) NCT01584648 (2) NCT02292654 (2) NCT03992456 (2) NCT03133546 (2) NCT01485809 (2) NCT01266967 (2) NCT02909712 (2) NCT00062764 (2) NCT01776684 (2) NCT03042221 (2) NCT01940809 (2) NCT01161537 (2) NCT01154816 (2) NCT01175759 (2) NCT01199731 (2) NCT02788058 (2) NCT03130452 (2) NCT01772732 (2) NCT02631447 (2) NCT02525692 (2) NCT02526537 (2) NCT03513666 (2) NCT02027961 (2) NCT03106779 (2) NCT04106544 (2) NCT04258943 (2) NCT00165984 (2) NCT00977470 (2) NCT02092974 (2) NCT03975231 (2) NCT01998295 (2) NCT03586453 (2) NCT02021305 (2) NCT03135197 (2) NCT00432016 (2) NCT03004625 (2) NCT03851445 (2) NCT04031898 (2) NCT04201418 (2) NCT01911507 (2) NCT03539224 (2) NCT01978236 (2) NCT00866177 (2) NCT00320879 (2) NCT00044304 (2) NCT01999179 (2) NCT00977730 (2) NCT02491775 (2) NCT00212147 (2) NCT02040064 (2) NCT00489385 (2) NCT01713023 (2) NCT04122729 (2) NCT03994393 (2) NCT02438722 (2) NCT02762448 (2) NCT00071903 (2) NCT00626223 (2) NCT01193829 (2) NCT03239340 (2) NCT02991274 (2) NCT02811354 (2) NCT03416530 (2) NCT02522988 (2) NCT00953706 (2) NCT02346955 (2) NCT03795688 (2) NCT02011945 (2) NCT00857675 (2) NCT00028262 (2) NCT02355431 (2) NCT02495233 (2) NCT04575415 (2) NCT03468985 (2) NCT00230087 (2) NCT02017600 (2) NCT04146298 (2) NCT02036359 (2) NCT04494789 (2) NCT00193947 (2) NCT02349633 (2) NCT02425397 (2) NCT04209816 (2) NCT00959504 (2) NCT03768908 (2) NCT04035486 (2) NCT04619004 (2) NCT00088803 (2) NCT00567359 (2) NCT04040829 (2) NCT02196181 (2) NCT04563871 (2) NCT02231775 (2) NCT03532698 (2) NCT03529084 (2) NCT03433469 (2) NCT02929693 (2) NCT04339829 (2) NCT03295396 (2) NCT03594916 (2) NCT03373760 (2) NCT01961830 (2) NCT02374645 (2) NCT03706287 (2) NCT04164901 (2) NCT03122717 (2) NCT04424966 (2) NCT02588261 (2) NCT01513174 (2) NCT03283826 (2) NCT02578004 (2) NCT00457821 (2) NCT02124044 (2) NCT02847377 (2) NCT03159117 (2) NCT03898908 (2) NCT03433833 (2) NCT02518802 (2) NCT01726738 (2) NCT00362687 (2) NCT03919474 (2) NCT02616393 (2) NCT02736513 (2) NCT02759614 (2) NCT01677741 (2) NCT02099058 (2) NCT02194881 (1) NCT03119831 (1) NCT01248936 (1) NCT03929458 (1) NCT03974022 (1) NCT03137264 (1) NCT01746277 (1) NCT01266369 (1) NCT03548064 (1) NCT01188785 (1) NCT01359436 (1) NCT02113878 (1) NCT03882281 (1) NCT03206372 (1) NCT01955681 (1) NCT03632317 (1) NCT01385722 (1) NCT03496766 (1) NCT02698748 (1) NCT03473665 (1) NCT01179828 (1) NCT01312337 (1) NCT03300414 (1) NCT02447939 (1) NCT02091999 (1) NCT04222283 (1) NCT01964131 (1) NCT03620318 (1) NCT01449461 (1) NCT04238624 (1) NCT01349660 (1) NCT02000726 (1) NCT00984360 (1) NCT01269424 (1) NCT00062907 (1) NCT04086680 (1) NCT00079326 (1) NCT02824952 (1) NCT02938520 (1) NCT01999270 (1) NCT01589302 (1) NCT00542841 (1) NCT00686270 (1) NCT00409175 (1) NCT01748019 (1) NCT03128749 (1) NCT02413736 (1) NCT01543113 (1) NCT00138684 (1) NCT02400437 (1) NCT04556305 (1) NCT02014909 (1) NCT03263364 (1) NCT03343197 (1) NCT03050437 (1) NCT01417442 (1) NCT00662688 (1) NCT03083769 (1) NCT02511340 (1) NCT03678506 (1) NCT02146365 (1) NCT04310943 (1) NCT02619955 (1) NCT02934139 (1) NCT00400387 (1) NCT00375219 (1) NCT00149305 (1) NCT03520946 (1) NCT02787447 (1) NCT04501614 (1) NCT03166631 (1) NCT04213313 (1) NCT02078531 (1) NCT02349048 (1) NCT02981784 (1) NCT01647711 (1) NCT03231722 (1) NCT03576937 (1) NCT04412070 (1) NCT00554866 (1) NCT03151161 (1) NCT01817166 (1) NCT02220855 (1) NCT02512627 (1) NCT04591197 (1) NCT03402048 (1) NCT04500704 (1) NCT02323724 (1) NCT01166126 (1) NCT03029858 (1) NCT04317599 (1) NCT00300573 (1) NCT00809211 (1) NCT01393730 (1) NCT02318368 (1) NCT02228369 (1) NCT01074398 (1) NCT04500717 (1) NCT03134131 (1) NCT01004497 (1) NCT02455167 (1) NCT02073279 (1) NCT02117817 (1) NCT00323687 (1) NCT01605981 (1) NCT01371955 (1) NCT04147767 (1) NCT04144257 (1) NCT03490123 (1) NCT04423185 (1) NCT02625337 (1) NCT03567629 (1) NCT03360929 (1) NCT00109278 (1) NCT04108156 (1) NCT02132598 (1) NCT00542451 (1) NCT01587573 (1) NCT00868465 (1) NCT01494402 (1) NCT00867139 (1) NCT03363139 (1) NCT01936051 (1) NCT02341131 (1) NCT00037076 (1) NCT00582907 (1) NCT02169869 (1) NCT03284684 (1) NCT04204473 (1) NCT01074359 (1) NCT01400191 (1) NCT04530565 (1) NCT03530319 (1) NCT04146402 (1) NCT02658682 (1) NCT04241835 (1) NCT03133234 (1) NCT02251535 (1) NCT00085111 (1) NCT02305095 (1) NCT01645124 (1) NCT03414450 (1) NCT02716246 (1) NCT02308137 (1) NCT04449874 (1) NCT00045942 (1) NCT04604067 (1) NCT03204500 (1) NCT02951052 (1) NCT00634595 (1) NCT03236584 (1) NCT03428178 (1) NCT02098954 (1) NCT04619563 (1) NCT02463513 (1) NCT03634059 (1) NCT03363217 (1) NCT04381650 (1) NCT00887562 (1) NCT01838941 (1) NCT03934372 (1) NCT04485507 (1) NCT03674502 (1) NCT02075840 (1) NCT01134120 (1) NCT01550640 (1) NCT00737126 (1) NCT00005543 (1) NCT02508532 (1) NCT02722057 (1) NCT02103257 (1) NCT01146132 (1) NCT03365882 (1) NCT00312039 (1) NCT02293733 (1) NCT00669669 (1) NCT01262352 (1) NCT03268161 (1) NCT03648268 (1) NCT03970447 (1) NCT01147445 (1) NCT02607124 (1) NCT03594422 (1) NCT01260181 (1) NCT03314272 (1) NCT03639714 (1) NCT00152061 (1) NCT04609319 (1) NCT00260897 (1) NCT04551521 (1) NCT00830245 (1) NCT01338025 (1) NCT00908687 (1) NCT01928940 (1) NCT03045991 (1) NCT03381066 (1) NCT01882205 (1) NCT00405249 (1) NCT04116502 (1) NCT04442815 (1) NCT04079179 (1) NCT01489592 (1) NCT01436656 (1) NCT02130466 (1) NCT02157922 (1) NCT00570401 (1) NCT01297452 (1) NCT01086267 (1) NCT02928224 (1) NCT01455389 (1) NCT02476851 (1) NCT02961270 (1) NCT02518737 (1) NCT04585750 (1) NCT01663857 (1) NCT02359747 (1) NCT00579683 (1) NCT03602027 (1) NCT01524757 (1) NCT04371848 (1) NCT04436848 (1) NCT02518750 (1) NCT00092391 (1) NCT02070549 (1) NCT00702403 (1) NCT03946748 (1) NCT03654508 (1) NCT04044430 (1) NCT03293524 (1) NCT04133948 (1) NCT00769587 (1) NCT01543035 (1) NCT04448158 (1) NCT00336076 (1) NCT02405247 (1) NCT01453595 (1) NCT03857243 (1) NCT01784939 (1) NCT02806362 (1) NCT00096746 (1) NCT01441128 (1) NCT02652585 (1) NCT03054038 (1) NCT00086957 (1) NCT03336463 (1) NCT00001566 (1) NCT04012866 (1) NCT01482923 (1) NCT03580655 (1) NCT04462471 (1) NCT04173507 (1) NCT01703962 (1) NCT01528774 (1) NCT04485559 (1) NCT00201214 (1) NCT00395629 (1) NCT03499743 (1) NCT04560413 (1) NCT02460068 (1) NCT01801904 (1) NCT00708162 (1) NCT04418167 (1) NCT03414814 (1) NCT04560894 (1) NCT02666755 (1) NCT02580435 (1) NCT01353625 (1) NCT00233285 (1) NCT01225887 (1) NCT01827436 (1) NCT03559699 (1) NCT03780738 (1) NCT01901432 (1) NCT02968303 (1) NCT01328210 (1) NCT00410202 (1) NCT02435927 (1) NCT02931487 (1) NCT01968551 (1) NCT00831974 (1) NCT04201405 (1) NCT02194049 (1) NCT01976104 (1) NCT01164891 (1) NCT02695290 (1) NCT02500147 (1) NCT03721120 (1) NCT01381289 (1) NCT01408589 (1) NCT04012411 (1) NCT02595944 (1) NCT03696355 (1) NCT03670186 (1) NCT01456650 (1) NCT03893357 (1) NCT02606253 (1) NCT03464201 (1) NCT03486496 (1) NCT03883100 (1) NCT00906087 (1) NCT03267654 (1) NCT04427072 (1) NCT02066038 (1) NCT04077372 (1) NCT02070536 (1) NCT02400853 (1) NCT03909334 (1) NCT00373425 (1) NCT03562819 (1) NCT01107418 (1) NCT03502330 (1) NCT03514784 (1) NCT04192292 (1) NCT01709292 (1) NCT02071862 (1) NCT01570699 (1) NCT02511288 (1) NCT02774278 (1) NCT00618423 (1) NCT00653666 (1) NCT00090493 (1) NCT01304602 (1) NCT03439865 (1) NCT04316546 (1) NCT01815255 (1) NCT02023710 (1) NCT04510220 (1) NCT03020095 (1) NCT02707445 (1) NCT01989585 (1) NCT03769103 (1) NCT01531673 (1) NCT01784419 (1) NCT02316496 (1) NCT02089555 (1) NCT02387216 (1) NCT00900185 (1) NCT02547675 (1) NCT04533321 (1) NCT01631279 (1) NCT03621540 (1) NCT01417520 (1) NCT00401999 (1) NCT02326285 (1) NCT04613596 (1) NCT01589445 (1) NCT03686085 (1) NCT01705626 (1) NCT00462943 (1) NCT02133144 (1) NCT01982955 (1) NCT04239833 (1) NCT04537715 (1) NCT01644591 (1) NCT01920204 (1) NCT03678454 (1) NCT00925002 (1) NCT03620669 (1) NCT00708695 (1) NCT01543698 (1) NCT01579630 (1) NCT02385461 (1) NCT03040986 (1) NCT01555697 (1) NCT00090454 (1) NCT02134015 (1) NCT03410160 (1) NCT00274261 (1) NCT04319614 (1) NCT03244956 (1) NCT02961608 (1) NCT01336634 (1) NCT01588145 (1) NCT04603326 (1) NCT01233752 (1) NCT03577314 (1) NCT00676117 (1) NCT02086487 (1) NCT03299049 (1) NCT04226950 (1) NCT02202200 (1) NCT03849768 (1) NCT02956278 (1) NCT02080715 (1) NCT03938012 (1) NCT02364999 (1) NCT04105153 (1) NCT01131325 (1) NCT01116193 (1) NCT01887587 (1) NCT02299622 (1) NCT00341120 (1) NCT03803553 (1) NCT01738555 (1) NCT02327169 (1) NCT02627664 (1) NCT02959749 (1) NCT02032680 (1) NCT00106977 (1) NCT02296125 (1) NCT03727763 (1) NCT03656627 (1) NCT01474551 (1) NCT04142554 (1) NCT01830244 (1) NCT01503164 (1) NCT04077892 (1) NCT00056550 (1) NCT02942095 (1) NCT00503971 (1) NCT03300115 (1) NCT04547946 (1) NCT04581824 (1) NCT02873832 (1) NCT02835599 (1) NCT03064516 (1) NCT00660361 (1) NCT03341494 (1) NCT04220801 (1) NCT04190628 (1) NCT03840915 (1) NCT03090815 (1) NCT00888134 (1) NCT01019655 (1) NCT03219970 (1) NCT02170961 (1) NCT02824458 (1) NCT00903292 (1) NCT01121575 (1) NCT00040157 (1) NCT00542789 (1) NCT02036177 (1) NCT00470171 (1) NCT01120262 (1) NCT00000912 (1) NCT01550380 (1) NCT04239443 (1) NCT01009814 (1) NCT04001803 (1) NCT00840190 (1) NCT00931762 (1) NCT02330367 (1) NCT00788762 (1) NCT02274337 (1) NCT02720822 (1) NCT00381654 (1) NCT00471497 (1) NCT02169973 (1) NCT01207440 (1) NCT01528085 (1) NCT03982134 (1) NCT01573494 (1) NCT02088645 (1) NCT03085485 (1) NCT03457220 (1) NCT01928576 (1) NCT02134886 (1) NCT01497626 (1) NCT00797238 (1) NCT04042701 (1) NCT04006249 (1) NCT02293460 (1) NCT04260022 (1) NCT00160888 (1) NCT02343666 (1) NCT03821363 (1) NCT00378469 (1) NCT00135447 (1) NCT03879629 (1) NCT04297748 (1) NCT02264990 (1) NCT00453609 (1) NCT00068913 (1) NCT04142190 (1) NCT03922061 (1) NCT03356548 (1) NCT02575560 (1) NCT03226223 (1) NCT00260000 (1) NCT02531685 (1) NCT02365441 (1) NCT03762590 (1) NCT03553329 (1) NCT02972333 (1) NCT04056910 (1) NCT02296996 (1) NCT03151096 (1) NCT02416739 (1) NCT02987829 (1) NCT00565461 (1) NCT02484404 (1) NCT03399669 (1) NCT00730574 (1) NCT00342056 (1) NCT02342353 (1) NCT01259050 (1) NCT03153293 (1) NCT03870828 (1) NCT00041457 (1) NCT02250326 (1) NCT03732703 (1) NCT03396185 (1) NCT03179436 (1) NCT03707756 (1) NCT00737178 (1) NCT04602897 (1) NCT02427893 (1) NCT01648998 (1) NCT02208843 (1) NCT02263638 (1) NCT00299949 (1) NCT01795131 (1) NCT03328078 (1) NCT00625560 (1) NCT04364230 (1) NCT02930954 (1) NCT04425681 (1) NCT02218632 (1) NCT03262779 (1) NCT03855696 (1) NCT00897091 (1) NCT03690115 (1) NCT03186196 (1) NCT01121172 (1) NCT02230267 (1) NCT02115386 (1) NCT01682083 (1) NCT01975727 (1) NCT03113604 (1) NCT04292938 (1) NCT00866762 (1) NCT02140333 (1) NCT02642042 (1) NCT01541813 (1) NCT01854294 (1) NCT02179814 (1) NCT01730599 (1) NCT02888977 (1) NCT02454933 (1) NCT03693170 (1) NCT01227577 (1) NCT03990181 (1) NCT01134484 (1) NCT04061980 (1) NCT01998841 (1) NCT03051282 (1) NCT04413201 (1) NCT03785249 (1) NCT03363347 (1) NCT01560104 (1) NCT00222677 (1) NCT04617002 (1) NCT01549314 (1) NCT02601950 (1) NCT01592136 (1) NCT03292133 (1) NCT01723800 (1) NCT01274208 (1) NCT03223155 (1) NCT00405587 (1) NCT00110513 (1) NCT04044170 (1) NCT02448251 (1) NCT02601937 (1) NCT04088188 (1) NCT02991898 (1) NCT01357941 (1) NCT01848873 (1) NCT01922076 (1) NCT03284502 (1) NCT04117945 (1) NCT00592540 (1) NCT00879632 (1) NCT01353534 (1) NCT01437618 (1) NCT03631706 (1) NCT03595644 (1) NCT04276415 (1) NCT02640287 (1) NCT00260520 (1) NCT04546282 (1) NCT01439802 (1) NCT01503502 (1) NCT02266641 (1) NCT03943394 (1) NCT04000529 (1) NCT04011293 (1) NCT02484365 (1) NCT03282305 (1) NCT03558607 (1) NCT02555566 (1) NCT03660696 (1) NCT02642016 (1) NCT02416232 (1) NCT03178071 (1) NCT00335244 (1) NCT02888990 (1) NCT00171912 (1) NCT00907699 (1) NCT02079298 (1) NCT02095782 (1) NCT01387763 (1) NCT03921151 (1) NCT04333472 (1) NCT01631708 (1) NCT02520934 (1) NCT03942094 (1) NCT01697163 (1) NCT00972751 (1) NCT01860534 (1) NCT02504489 (1) NCT01719367 (1) NCT04438902 (1) NCT03132779 (1) NCT03859531 (1) NCT03831646 (1) NCT04487873 (1) NCT02214615 (1) NCT02078388 (1) NCT02690519 (1) NCT03705195 (1) NCT03455829 (1) NCT02260505 (1) NCT01352637 (1) NCT03169127 (1) NCT02639273 (1) NCT04322383 (1) NCT02763098 (1) NCT03551626 (1) NCT03106012 (1) NCT03092674 (1) NCT00154960 (1) NCT03653546 (1) NCT02553811 (1) NCT04098393 (1) NCT00070473 (1) NCT04606771 (1) NCT01618383 (1) NCT01351324 (1) NCT03711422 (1) NCT00129532 (1) NCT03885830 (1) NCT03731013 (1) NCT04507919 (1) NCT01956227 (1) NCT00362466 (1) NCT04534283 (1) NCT03227926 (1) NCT04233346 (1) NCT03991403 (1) NCT01594723 (1) NCT00772876 (1) NCT04138485 (1) NCT01105169 (1) NCT00593476 (1) NCT01699711 (1) NCT02576080 (1) NCT03916185 (1) NCT01877811 (1) NCT01949909 (1) NCT03140761 (1) NCT03492801 (1) NCT03475004 (1) NCT01875653 (1) NCT03977584 (1) NCT02979769 (1) NCT04324112 (1) NCT02398825 (1) NCT01523171 (1) NCT03235505 (1) NCT04140305 (1) NCT00827138 (1) NCT03943342 (1) NCT00632632 (1) NCT01349465 (1) NCT01641107 (1) NCT02815137 (1) NCT03405194 (1) NCT01888926 (1) NCT01108627 (1) NCT03787056 (1) NCT04525768 (1) NCT01275196 (1) NCT02633943 (1) NCT01513356 (1) NCT02350426 (1) NCT02143050 (1) NCT03198897 (1) NCT04541082 (1) NCT03975114 (1) NCT02786381 (1) NCT00896727 (1) NCT02707562 (1) NCT03349931 (1) NCT02842177 (1) NCT03482362 (1) NCT02469974 (1) NCT03721289 (1) NCT03812172 (1) NCT01730911 (1) NCT00752076 (1) NCT04467853 (1) NCT04603885 (1) NCT01105351 (1) NCT02468661 (1) NCT01599364 (1) NCT00126880 (1) NCT00986765 (1) NCT04553081 (1) NCT01259817 (1) NCT01859182 (1) NCT03444090 (1) NCT03190941 (1) NCT02145234 (1) NCT03804528 (1) NCT04006301 (1) NCT00001721 (1) NCT03312634 (1) NCT04120454 (1) NCT02652780 (1) NCT00559026 (1) NCT01955421 (1) NCT03423186 (1) NCT03783975 (1) NCT03207009 (1) NCT00757783 (1) NCT03275597 (1) NCT02672358 (1) NCT00948467 (1) NCT02331966 (1) NCT01738867 (1) NCT02652767 (1) NCT02303041 (1) NCT03874455 (1) NCT02419287 (1) NCT02855047 (1) NCT01667562 (1) NCT02766335 (1) NCT03349983 (1) NCT04278027 (1) NCT03941782 (1) NCT01189435 (1) NCT04242069 (1) NCT01639092 (1) NCT02146118 (1) NCT03727867 (1) NCT00003970 (1) NCT00190177 (1) NCT02025829 (1) NCT02052193 (1) NCT03126799 (1) NCT01949194 (1) NCT02847429 (1) NCT04425187 (1) NCT01121419 (1) NCT03227029 (1) NCT04438005 (1) NCT04329325 (1) NCT00570297 (1) NCT02043223 (1) NCT03348631 (1) NCT03861156 (1) NCT01660906 (1) NCT02455362 (1) NCT01326741 (1) NCT04338243 (1) NCT03206112 (1) NCT00606307 (1) NCT00586651 (1) NCT03217253 (1) NCT00700414 (1) NCT01141023 (1) NCT02247687 (1) NCT03325517 (1) NCT00603265 (1) NCT02099214 (1) NCT02949843 (1) NCT03853551 (1) NCT00130078 (1) NCT01043874 (1) NCT03647657 (1) NCT01377025 (1) NCT03581292 (1) NCT04487080 (1) NCT00867334 (1) NCT04285671 (1) NCT03422237 (1) NCT03415126 (1) NCT03136562 (1) NCT03770273 (1) NCT02953522 (1) NCT00879307 (1) NCT03217669 (1) NCT01413685 (1) NCT04487093 (1) NCT02311998 (1) NCT02146963 (1) NCT01534897 (1) NCT03466268 (1) NCT01181505 (1) NCT00562276 (1) NCT01941654 (1) NCT02877212 (1) NCT01136967 (1) NCT02064569 (1) NCT03760458 (1) NCT02651844 (1) NCT04585035 (1) NCT01942993 (1) NCT02284633 (1) NCT03608046 (1) NCT03420079 (1) NCT04330326 (1) NCT00802841 (1) NCT01470209 (1) NCT03457337 (1) NCT04483947 (1) NCT02097472 (1) NCT01411046 (1) NCT01992029 (1) NCT02391623 (1) NCT03594162 (1) NCT01096368 (1) NCT02227693 (1) NCT03122366 (1) NCT01345877 (1) NCT02451852 (1) NCT02886195 (1) NCT01720758 (1) NCT00493103 (1) NCT03585686 (1) NCT03962647 (1) NCT04084249 (1) NCT01734915 (1) NCT00813514 (1) NCT02101684 (1) NCT03272464 (1) NCT03787992 (1) NCT02206763 (1) NCT00553332 (1) NCT01040338 (1) NCT03459534 (1) NCT01950585 (1) NCT01540253 (1) NCT02596113 (1) NCT00880321 (1) NCT00028366 (1) NCT03309462 (1) NCT00540046 (1) NCT01881984 (1) NCT03016377 (1) NCT00000838 (1) NCT01173913 (1) NCT02625519 (1) NCT02649972 (1) NCT03854474 (1) NCT02600260 (1) NCT03023904 (1) NCT03472508 (1) NCT01368523 (1) NCT02960230 (1) NCT02122588 (1) NCT04250545 (1) NCT00262327 (1) NCT00335868 (1) NCT01717105 (1) NCT02357732 (1) NCT00533754 (1) NCT03285750 (1) NCT01584297 (1) NCT03377556 (1) NCT01583322 (1) NCT03227861 (1) NCT02106546 (1) NCT00285909 (1) NCT02114177 (1) NCT01740297 (1) NCT02323100 (1) NCT00280215 (1) NCT01089101 (1) NCT03435939 (1) NCT00957411 (1) NCT02370329 (1) NCT02489903 (1) NCT02956993 (1) NCT04539678 (1) NCT04146181 (1) NCT00875342 (1) NCT02161380 (1) NCT03765775 (1) NCT01283048 (1) NCT04590833 (1) NCT01276743 (1) NCT01402609 (1) NCT02052934 (1) NCT02428543 (1) NCT02311569 (1) NCT01283035 (1) NCT03720873 (1) NCT03189030 (1) NCT00623220 (1) NCT02252146 (1) NCT03176199 (1) NCT00878826 (1) NCT00740545 (1) NCT01871740 (1) NCT02037308 (1) NCT02819804 (1) NCT03455556 (1) NCT01400451 (1) NCT03203850 (1) NCT03718104 (1) NCT01719250 (1) NCT00216099 (1) NCT04229537 (1) NCT03794297 (1) NCT04271072 (1) NCT01524549 (1) NCT01769911 (1) NCT02454842 (1) NCT01762046 (1) NCT03213652 (1) NCT02569827 (1) NCT03406104 (1) NCT02906202 (1) NCT03117049 (1) NCT03877055 (1) NCT04527666 (1) NCT02989857 (1) NCT01586403 (1) NCT01659151 (1) NCT02504346 (1) NCT02725333 (1) NCT02323126 (1) NCT04426825 (1) NCT01069939 (1) NCT02514174 (1) NCT01227889 (1) NCT01699698 (1) NCT02906696 (1) NCT00878891 (1) NCT03647592 (1) NCT03615105 (1) NCT01013987 (1) NCT04549428 (1) NCT03865082 (1) NCT01670396 (1) NCT03568773 (1) NCT04620330 (1) NCT01352585 (1) NCT02865304 (1) NCT00957476 (1) NCT02186236 (1) NCT01594476 (1) NCT00684307 (1) NCT00005332 (1) NCT02428101 (1) NCT01045525 (1) NCT04609566 (1) NCT02311140 (1) NCT02322255 (1) NCT01744665 (1) NCT01893554 (1) NCT01951924 (1) NCT01390818 (1) NCT01816984 (1) NCT03225664 (1) NCT04452877 (1) NCT02339922 (1) NCT01067781 (1) NCT01858389 (1) NCT03381274 (1) NCT03007043 (1) NCT00874419 (1) NCT00405054 (1) NCT01466660 (1) NCT00873574 (1) NCT03754244 (1) NCT00255658 (1) NCT03845920 (1) NCT02200562 (1) NCT02722668 (1) NCT04391283 (1) NCT00966771 (1) NCT03549689 (1) NCT04489706 (1) NCT04120883 (1) NCT01002898 (1) NCT02151981 (1) NCT02857270 (1) NCT02109653 (1) NCT02960607 (1) NCT01707290 (1) NCT04499989 (1) NCT03020004 (1) NCT04043338 (1) NCT03523065 (1) NCT00723567 (1) NCT00899743 (1) NCT02060526 (1) NCT01362348 (1) NCT03944356 (1) NCT00694161 (1) NCT00522145 (1) NCT03224767 (1) NCT04194203 (1) NCT01669811 (1) NCT03788460 (1) NCT04388904 (1) NCT04075396 (1) NCT02151526 (1) NCT03595917 (1) NCT04092725 (1) NCT01264380 (1) NCT03698318 (1) NCT04104399 (1) NCT03158389 (1) NCT04526782 (1) NCT01254188 (1) NCT02870244 (1) NCT03745326 (1) NCT00003567 (1) NCT03911440 (1) NCT01504542 (1) NCT04480918 (1) NCT00747994 (1) NCT03621865 (1) NCT01281722 (1) NCT02410863 (1) NCT00463385 (1) NCT03243461 (1) NCT01665417 (1) NCT02779530 (1) NCT01837017 (1) NCT02488694 (1) NCT02789345 (1) NCT02924935 (1) NCT03612908 (1) NCT03736837 (1) NCT03110822 (1) NCT03130894 (1) NCT02380157 (1) NCT03818763 (1) NCT02480725 (1) NCT02534168 (1) NCT01259856 (1) NCT04151563 (1) NCT00595517 (1) NCT01745120 (1) NCT02425904 (1) NCT02463383 (1) NCT03965689 (1) NCT04258956 (1) NCT02953496 (1) NCT04034459 (1) NCT03778229 (1) NCT01750918 (1) NCT03386942 (1) NCT01038856 (1) NCT02631876 (1) NCT03862885 (1) NCT01233219 (1) NCT01597908 (1) NCT03859245 (1) NCT02609984 (1) NCT04592666 (1) NCT04442672 (1) NCT02885766 (1) NCT00854841 (1) NCT04034446 (1) NCT04206072 (1) NCT00607581 (1) NCT00893178 (1) NCT01956786 (1) NCT04196413 (1) NCT00806325 (1) NCT00364728 (1) NCT04439279 (1) NCT01705847 (1) NCT02561988 (1) NCT04123626 (1) NCT03417830 (1) NCT02922296 (1) NCT01243372 (1) NCT03453918 (1) NCT00513110 (1) NCT04165031 (1) NCT04225429 (1) NCT01006980 (1) NCT00352053 (1) NCT02338011 (1) NCT04360005 (1) NCT02777567 (1) NCT04591002 (1) NCT02367859 (1) NCT03647956 (1) NCT04293562 (1) NCT02628314 (1) NCT03303833 (1) NCT01460134 (1) NCT02929706 (1) NCT03342170 (1) NCT04042558 (1) NCT02626130 (1) NCT03232307 (1) NCT00435513 (1) NCT01391260 (1) NCT02317562 (1) NCT01980550 (1) NCT02561533 (1) NCT00092404 (1) NCT03758677 (1) NCT01001273 (1) NCT03438318 (1) NCT02318407 (1) NCT02422797 (1) NCT02538926 (1) NCT02615015 (1) NCT01284712 (1) NCT04316351 (1) NCT03091491 (1) NCT01740648 (1) NCT01866410 (1) NCT01175161 (1) NCT01602939 (1) NCT04330664 (1) NCT01701037 (1) NCT03612869 (1) NCT00753480 (1) NCT00090688 (1) NCT01717404 (1) NCT03590522 (1) NCT02937727 (1) NCT03899857 (1) NCT04133870 (1) NCT03790397 (1) NCT03024281 (1) NCT03389256 (1) NCT03426371 (1) NCT02926638 (1) NCT04193553 (1) NCT00997334 (1) NCT04544202 (1) NCT04201457 (1) NCT00618631 (1) NCT04455594 (1) NCT03439215 (1) NCT02164916 (1) NCT02000882 (1) NCT01897116 (1) NCT03264794 (1) NCT03810066 (1) NCT00125489 (1) NCT04372498 (1) NCT02788669 (1) NCT00367952 (1) NCT00977756 (1) NCT03387072 (1) NCT01586195 (1) NCT02611492 (1) NCT01220648 (1) NCT01708954 (1) NCT01967940 (1) NCT03758287 (1) NCT02392871 (1) NCT04401059 (1) NCT02869932 (1) NCT00716014 (1) NCT01526928 (1) NCT00930215 (1) NCT03228667 (1) NCT04273581 (1) NCT00980018 (1) NCT04557956 (1) NCT01898039 (1) NCT03883087 (1) NCT04364451 (1) NCT04216524 (1) NCT04204551 (1) NCT03672968 (1) NCT03924050 (1) NCT03983252 (1) NCT01639872 (1) NCT02747277 (1) NCT04116918 (1) NCT00669396 (1) NCT02153398 (1) NCT03543306 (1) NCT01377376 (1) NCT01603446 (1) NCT01534520 (1) NCT01972529 (1) NCT01731704 (1) NCT04186377 (1) NCT01424475 (1) NCT02066636 (1) NCT01748149 (1) NCT02467270 (1) NCT02092909 (1) NCT02864251 (1) NCT03846427 (1) NCT03779191 (1) NCT00055848 (1) NCT01217437 (1) NCT04088734 (1) NCT03191786 (1) NCT01450319 (1) NCT03652090 (1) NCT00995553 (1) NCT01833572 (1) NCT00432900 (1) NCT03553563 (1) NCT01878006 (1) NCT03357627 (1) NCT03668431 (1) NCT03832257 (1) NCT02739243 (1) NCT01193881 (1) NCT02427620 (1) NCT03784599 (1) NCT02055976 (1) NCT02147990 (1) NCT01400074 (1) NCT01551030 (1) NCT00617708 (1) NCT00050180 (1) NCT00283387 (1) NCT03310541 (1) NCT00931944 (1) NCT02717455 (1) NCT02730884 (1) NCT00532792 (1) NCT04099836 (1) NCT02375022 (1) NCT02074696 (1) NCT03709706 (1) NCT00020787 (1) NCT01739231 (1) NCT04399551 (1) NCT02590952 (1) NCT02063971 (1) NCT04254419 (1) NCT01683175 (1) NCT03373370 (1) NCT00814073 (1) NCT02417740 (1) NCT03374215 (1) NCT02783300 (1) NCT03053219 (1) NCT01595425 (1) NCT04128878 (1) NCT01101438 (1) NCT00769067 (1) NCT02580708 (1) NCT03764553 (1) NCT03344809 (1) NCT04009148 (1) NCT02094222 (1) NCT02178722 (1) NCT03452150 (1) NCT04390243 (1) NCT00751777 (1) NCT00173069 (1) NCT02404441 (1) NCT02311478 (1) NCT01339052 (1) NCT04059874 (1) NCT01833143 (1) NCT00270556 (1) NCT02746341 (1) NCT02770014 (1) NCT02977780 (1) NCT01728025 (1) NCT03866499 (1) NCT03107156 (1) NCT01172509 (1) NCT01822496 (1) NCT04171284 (1) NCT03020797 (1) NCT03856697 (1) NCT02705846 (1) NCT04552769 (1) NCT00428441 (1) NCT02690324 (1) NCT03521154 (1) NCT01453036 (1) NCT01937325 (1) NCT04206787 (1) NCT04230473 (1) NCT02383524 (1) NCT04528680 (1) NCT01663545 (1) NCT04083976 (1) NCT01754376 (1) NCT01262482 (1) NCT01074177 (1) NCT00634673 (1) NCT02141464 (1) NCT01999985 (1) NCT02670707 (1) NCT01363570 (1) NCT01586520 (1) NCT03067415 (1) NCT03173820 (1) NCT00155207 (1) NCT01487291 (1) NCT02630264 (1) NCT03257124 (1) NCT01744561 (1) NCT01872780 (1) NCT02762877 (1) NCT04262466 (1) NCT01139970 (1) NCT02655536 (1) NCT02785939 (1) NCT00588263 (1) NCT01435655 (1) NCT03919071 (1) NCT00668421 (1) NCT03236675 (1) NCT03224208 (1) NCT01711632 (1) NCT02429791 (1) NCT03521596 (1) NCT02274012 (1) NCT03101813 (1) NCT00029627 (1) NCT03701815 (1) NCT03001609 (1) NCT01141829 (1) NCT04148898 (1) NCT00443612 (1) NCT02081378 (1) NCT00612898 (1) NCT03972943 (1) NCT02785952 (1) NCT00708929 (1) NCT03615443 (1) NCT03548220 (1) NCT01756118 (1) NCT03807778 (1) NCT00671138 (1) NCT00749853 (1) NCT01582997 (1) NCT00815321 (1) NCT01398644 (1) NCT03236610 (1) NCT03053297 (1) NCT02590588 (1) NCT02125357 (1) NCT00245986 (1) NCT04505956 (1) NCT01341743 (1) NCT01339442 (1) NCT02833194 (1) NCT02403193 (1) NCT02630212 (1) NCT00647946 (1) NCT02408887 (1) NCT04396860 (1) NCT01237522 (1) NCT02474355 (1) NCT01761968 (1) NCT03731260 (1) NCT02091141 (1) NCT04311034 (1) NCT01063933 (1) NCT03890198 (1) NCT01789060 (1) NCT03168074 (1) NCT03215706 (1) NCT03588273 (1) NCT02387957 (1) NCT01299337 (1) NCT03046992 (1) NCT04148066 (1) NCT00173446 (1) NCT02422719 (1) NCT02754362 (1) NCT03160105 (1) NCT01159145 (1) NCT02782403 (1) NCT02838420 (1) NCT00794885 (1) NCT04410796 (1) NCT04143607 (1) NCT04358562 (1) NCT04306926 (1) NCT01810965 (1) NCT00433862 (1) NCT00949702 (1) NCT01744171 (1) NCT02314143 (1) NCT02713880 (1) NCT02199613 (1) NCT00687518 (1) NCT02923986 (1) NCT04325698 (1) NCT01014546 (1) NCT04568239 (1) NCT01700582 (1) NCT00672035 (1) NCT03115164 (1) NCT01068327 (1) NCT00464113 (1) NCT01933347 (1) NCT03452592 (1) NCT01120964 (1) NCT02186301 (1) NCT01791309 (1) NCT00644878 (1) NCT02550990 (1) NCT02965378 (1) NCT03842969 (1) NCT03952052 (1) NCT04484142 (1) NCT01396408 (1) NCT01274091 (1) NCT02117336 (1) NCT02412943 (1) NCT04607421 (1) NCT01861223 (1) NCT00089297 (1) NCT00570583 (1) NCT01245556 (1) NCT02292732 (1) NCT03087071 (1) NCT02034110 (1) NCT03716908 (1)

SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT02070549

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I Trial of Single Agent Trametinib (GSK1120212) in Advanced Cancer Patients With Hepatic Dysfunction

This phase I trial studies the side effects and best dose of trametinib in treating patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) with or without liver (hepatic) dysfunction. Trametinib may stop the growth of tumor cells by blocking proteins needed for cell growth. When these proteins are blocked, the growth of cancer cells may be stopped and the cancer cells will then die. Hepatic dysfunction is frequently found in patients with advanced cancer and usually prevents patients from receiving standard treatments or from participating in clinical trials. Patients may also need dose adjustments or absorb drugs differently. Trametinib may be a better treatment for patients with advanced cancers and hepatic dysfunction.

NCT02070549 Advanced Malignant Solid Neoplasm Metastatic Malignant Neoplasm in the Liver Metastatic Malignant Solid Neoplasm Unresectable Solid Neoplasm
MeSH:Neoplasms
HPO:Neoplasm

1 Interventions

Name: Trametinib

Description: Given PO
Type: Drug
Group Labels: 1

Treatment (trametinib)


Primary Outcomes

Description: Dose escalation and determination of the maximum tolerated dose will be carried out separately for each cohort or stratum. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

Measure: Maximum tolerated dose of trametinib

Time: 28 days

Description: Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

Measure: Dose-limiting toxicity

Time: 28 days

Description: Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

Measure: Pharmacokinetic profile of trametinib

Time: Baseline and 0.5, 1, 2, 3, 4, 6, 10, and 24 hours on days 15 and 16 of cycle 1

Secondary Outcomes

Description: Will document in patients with varying degrees of hepatic dysfunction.

Measure: Non-dose-limiting toxicities associated with the administration of trametinib

Time: Up to 4 weeks post treatment

Description: Will be assessed using the Response Evaluation Criteria in Solid Tumors criteria 1.1. Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics.

Measure: Objective response to treatment

Time: Up to 4 weeks post treatment

Description: Will be assessed by utilizing genomic sequencing technologies. Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships.

Measure: Predictive biomarkers for individual cancer patients

Time: Up to 4 weeks post treatment

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 V600E

Descriptive statistics and plotting of data will also be used to better understand potential relationships.. Inclusion Criteria: - Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective - Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment - Based on recent data that have shown limited trametinib benefit, patients with the following tumor types will be excluded from the normal and mild cohorts: - Pancreatic cancer patients - Colorectal cancer patients - BRAF V600E melanoma patients who have failed BRAF inhibitors - Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist - All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon >= 28 days before study entry - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 (except alopecia) at the time of enrollment - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L - Hemoglobin >= 9 g/dL - Platelets >= 75 x 10^9/L - Serum creatinine =< 1.5 mg/dL (=< 133 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min - Proteinuria =< +1 on dipstick or =< 1 gram/24 hours - Prothrombin time (PT) =< 1.5 x institutional upper limit of normal (ULN) - International normalized ratio (INR) =< 1.5 x institutional ULN - Partial thromboplastin time (PTT) =< 1.5 x institutional ULN - Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) - No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes - Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below: - Group A: Normal hepatic function - Bilirubin =< ULN - Aspartate aminotransferase (AST) =< ULN - Group B: Mild hepatic dysfunction - B1: bilirubin =< ULN and AST > ULN - B2: ULN < bilirubin =< 1.5 x ULN and any AST - Group C: Moderate hepatic dysfunction - 1.5 x ULN < bilirubin =< 3 x ULN and any AST - Group D: Severe hepatic dysfunction - 3 x ULN < bilirubin =< 10 x ULN and any AST; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Patients with active hemolysis should be excluded. --- V600E ---

Descriptive statistics and plotting of data will also be used to better understand potential relationships.. Inclusion Criteria: - Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective - Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment - Based on recent data that have shown limited trametinib benefit, patients with the following tumor types will be excluded from the normal and mild cohorts: - Pancreatic cancer patients - Colorectal cancer patients - BRAF V600E melanoma patients who have failed BRAF inhibitors - Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist - All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon >= 28 days before study entry - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 (except alopecia) at the time of enrollment - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L - Hemoglobin >= 9 g/dL - Platelets >= 75 x 10^9/L - Serum creatinine =< 1.5 mg/dL (=< 133 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min - Proteinuria =< +1 on dipstick or =< 1 gram/24 hours - Prothrombin time (PT) =< 1.5 x institutional upper limit of normal (ULN) - International normalized ratio (INR) =< 1.5 x institutional ULN - Partial thromboplastin time (PTT) =< 1.5 x institutional ULN - Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) - No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes - Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below: - Group A: Normal hepatic function - Bilirubin =< ULN - Aspartate aminotransferase (AST) =< ULN - Group B: Mild hepatic dysfunction - B1: bilirubin =< ULN and AST > ULN - B2: ULN < bilirubin =< 1.5 x ULN and any AST - Group C: Moderate hepatic dysfunction - 1.5 x ULN < bilirubin =< 3 x ULN and any AST - Group D: Severe hepatic dysfunction - 3 x ULN < bilirubin =< 10 x ULN and any AST; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Patients with active hemolysis should be excluded. --- V600E --- --- V600E ---

Hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Trametinib can cause fetal harm when administered to a pregnant woman; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - History of another malignancy - Exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above - History of interstitial lung disease or pneumonitis - Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 28 days prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrollment - Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the study; patients previously treated with v-raf murine sarcoma (RAF) and/or mitogen-activated protein kinase (MEK) inhibitors are excluded from the study; multikinase antiangiogenic tyrosine kinase inhibitors such as regorafenib, sorafenib, sunitinib, etc. whose primary mechanism of action is not RAF inhibition, are allowed; if there are any questions, please contact study's principal investigator - Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression - Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or excipients or to dimethyl sulfoxide (DMSO) - Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: - Other anti-cancer therapy while on study treatment; (Note: megestrol [Megace] if used as an appetite stimulant is allowed) - Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) - History or current evidence/risk of retinal vein occlusion (RVO) - History or evidence of cardiovascular risk including any of the following: - LVEF < LLN - A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec - History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible) - History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization - History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system - Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy - Patients with intra-cardiac defibrillators - Known cardiac metastases - Active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible) - Patients with known human immunodeficiency virus (HIV) infection are eligible if not on antiviral agents and cluster of differentiation (CD)4 counts are adequate (>= 500) - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Animal reproductive studies have not been conducted with trametinib; therefore, the study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable) - HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated - Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk Inclusion Criteria: - Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective - Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment - Based on recent data that have shown limited trametinib benefit, patients with the following tumor types will be excluded from the normal and mild cohorts: - Pancreatic cancer patients - Colorectal cancer patients - BRAF V600E melanoma patients who have failed BRAF inhibitors - Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist - All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon >= 28 days before study entry - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 (except alopecia) at the time of enrollment - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L - Hemoglobin >= 9 g/dL - Platelets >= 75 x 10^9/L - Serum creatinine =< 1.5 mg/dL (=< 133 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min - Proteinuria =< +1 on dipstick or =< 1 gram/24 hours - Prothrombin time (PT) =< 1.5 x institutional upper limit of normal (ULN) - International normalized ratio (INR) =< 1.5 x institutional ULN - Partial thromboplastin time (PTT) =< 1.5 x institutional ULN - Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) - No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes - Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below: - Group A: Normal hepatic function - Bilirubin =< ULN - Aspartate aminotransferase (AST) =< ULN - Group B: Mild hepatic dysfunction - B1: bilirubin =< ULN and AST > ULN - B2: ULN < bilirubin =< 1.5 x ULN and any AST - Group C: Moderate hepatic dysfunction - 1.5 x ULN < bilirubin =< 3 x ULN and any AST - Group D: Severe hepatic dysfunction - 3 x ULN < bilirubin =< 10 x ULN and any AST; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Patients with active hemolysis should be excluded. --- V600E ---

Hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Trametinib can cause fetal harm when administered to a pregnant woman; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - History of another malignancy - Exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above - History of interstitial lung disease or pneumonitis - Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 28 days prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrollment - Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the study; patients previously treated with v-raf murine sarcoma (RAF) and/or mitogen-activated protein kinase (MEK) inhibitors are excluded from the study; multikinase antiangiogenic tyrosine kinase inhibitors such as regorafenib, sorafenib, sunitinib, etc. whose primary mechanism of action is not RAF inhibition, are allowed; if there are any questions, please contact study's principal investigator - Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression - Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or excipients or to dimethyl sulfoxide (DMSO) - Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: - Other anti-cancer therapy while on study treatment; (Note: megestrol [Megace] if used as an appetite stimulant is allowed) - Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) - History or current evidence/risk of retinal vein occlusion (RVO) - History or evidence of cardiovascular risk including any of the following: - LVEF < LLN - A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec - History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible) - History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization - History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system - Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy - Patients with intra-cardiac defibrillators - Known cardiac metastases - Active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible) - Patients with known human immunodeficiency virus (HIV) infection are eligible if not on antiviral agents and cluster of differentiation (CD)4 counts are adequate (>= 500) - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Animal reproductive studies have not been conducted with trametinib; therefore, the study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable) - HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated - Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk Inclusion Criteria: - Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective - Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment - Based on recent data that have shown limited trametinib benefit, patients with the following tumor types will be excluded from the normal and mild cohorts: - Pancreatic cancer patients - Colorectal cancer patients - BRAF V600E melanoma patients who have failed BRAF inhibitors - Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist - All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon >= 28 days before study entry - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 (except alopecia) at the time of enrollment - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L - Hemoglobin >= 9 g/dL - Platelets >= 75 x 10^9/L - Serum creatinine =< 1.5 mg/dL (=< 133 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min - Proteinuria =< +1 on dipstick or =< 1 gram/24 hours - Prothrombin time (PT) =< 1.5 x institutional upper limit of normal (ULN) - International normalized ratio (INR) =< 1.5 x institutional ULN - Partial thromboplastin time (PTT) =< 1.5 x institutional ULN - Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) - No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes - Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below: - Group A: Normal hepatic function - Bilirubin =< ULN - Aspartate aminotransferase (AST) =< ULN - Group B: Mild hepatic dysfunction - B1: bilirubin =< ULN and AST > ULN - B2: ULN < bilirubin =< 1.5 x ULN and any AST - Group C: Moderate hepatic dysfunction - 1.5 x ULN < bilirubin =< 3 x ULN and any AST - Group D: Severe hepatic dysfunction - 3 x ULN < bilirubin =< 10 x ULN and any AST; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results - Patients with active hemolysis should be excluded. --- V600E --- --- V600E ---



HPO Nodes


HPO:
HP:0002664: Neoplasm
Genes 1537
H19 RPS19 WT1 GPR101 CHEK2 MYD88 VEGFC PGM3 CTNNB1 PDGFRA IRF1 RHBDF2 PICALM FANCC GDNF RET PRKAR1A NELFA BCL10 KRT10 BLK TINF2 SMARCD2 NSD2 BRCA1 KRAS TRIP13 KCNH1 PERP CDH23 IKBKG MCC JAK2 MET GTF2E2 FOXC2 NF1 RAD51 TP53 ERCC4 WNT10A ASXL1 CTLA4 FLT4 DVL3 BRCA1 MLH3 NSD1 ERCC2 TSC2 FANCL RPS14 CDC73 TNFRSF4 STAG3 MSTO1 AIP EVC RET PLCD1 SDHB NEK1 POLH ASXL1 BRAF IL7 MAP2K1 ARSA BRAF COL4A5 CYLD KRT14 MLLT10 RASGRP1 H19 XIAP NTHL1 FGFR2 IGH DNAJC21 LETM1 MCM4 MYF6 CD70 FAM149B1 FGFR3 TERF2IP TNFRSF13C GLI3 DDX41 RPL26 PRLR SBDS LIG4 MGMT RERE KLLN FANCM WT1 PHB AXIN2 KIT PTEN TGFBR2 GJA1 PDGFRL STAT6 TYR CPLANE1 IFNG SIX6 JAG1 PALB2 SSX1 FANCG KIT MYO1H ELANE RPS19 H19-ICR KRT6B IDH2 PLCB4 FGFR1 BAP1 MINPP1 MST1 SMARCB1 PDGFRB RB1 FAT4 NF1 HFE SDHD WT1 TET2 BMPR1A RAF1 POLR1D CBFB SKIV2L IRF1 COL18A1 HMBS RET MMEL1 IGF2R JAK2 SEC23A BUB1B XPC ING1 AXIN2 KIT PALB2 MAGT1 STAC3 ALK SLC25A13 TMEM231 SHOX TDGF1 REST SMO SMARCA4 DNM2 TSR2 LIN28B GNAS WT1 CDKN1A DNAJC21 DKC1 BAP1 SRGAP1 ALX1 PTPN11 CBL APC SCN11A MAP3K1 RPL10 KLF6 PAX7 APC C1S NRTN BUB3 KRT5 LIG4 CARD14 GNAS MLH1 CDKN2A GNA11 TMEM127 ESR1 IL2RG KRT1 MET NF2 SDHAF2 SDHD WT1 MAP3K8 STAT1 PHOX2B PTPRJ PTCH2 CHD7 TERT LMNA ERCC6 EDNRB XPA PDGFRA OFD1 VHL SAMD9L SF3B1 FERMT1 BRCA1 GDF2 CASP8 TP53 LAMC2 GFI1B FANCD2 PYGL CR2 AR REST APPL1 APC CYP2A6 SEMA3C WT1 CDKN2A CTSA LRRC8A PHOX2B SMARCB1 NAGS FLI1 SOX2 RAD21 TMEM127 APC FGF3 BAP1 BUB1 RAD51 DKC1 RAD54B VHL EPCAM ASXL1 SRC HRAS BMP2 SLC25A11 PTH1R KRAS MYD88 NPM1 PTEN SH3GL1 PHOX2B TP53 SMAD4 XPA GATA4 MLH1 PMS2 STK11 FANCC DHCR7 PTCH1 CDC73 CYLD MEN1 CLCNKB CHEK2 RNF139 HABP2 POLE H19-ICR MMP1 RPL27 CC2D2A PIK3CA GPC3 ABL1 PALLD WASHC5 INTU ERCC5 DYNC2LI1 SLC22A18 TP53 CDH1 SHH MPL AKT1 NFKB2 NRAS PIGL CASP8 MYC KCNE3 DLST TAF15 TNFRSF13B GDNF EYA1 APC2 TNFRSF1B TCTN3 PPOX PNP PKHD1 BLM ODC1 IL12A TERT STK11 KRT17 IDH1 CIB1 RPL18 DVL1 ARHGAP26 PHOX2B CASP8 RPGRIP1L KRT6A SDHB FGFR2 VAMP7 JAK2 SRY DNMT3A EPAS1 KCNQ1OT1 MSH6 KRAS SDHB WNT5A DNMT3A RUNX1 TRIM28 DHCR24 USB1 VANGL2 GCM2 LIG4 KRAS SDHB ENG SEMA3D TRNS2 MINPP1 CASP10 NTHL1 LMOD1 SUFU FOXH1 CD81 ALX4 F13B BMPR1B RB1 CACNA1S CHIC2 VHL HRAS KIF11 KCNJ11 WRN SLC37A4 GNAQ LZTR1 CCND1 CPLX1 NR4A3 RYR1 NBEAL2 GATA2 TP63 APC KRAS HNF1B SUFU GNB1 MSX2 GPC3 CEL TCTN3 OCA2 MDM4 RB1 TMC6 ASCL1 AR BRIP1 CHEK2 AAGAB TSC1 TXNRD2 POLD1 CARMIL2 APC PIK3CA AKT1 POLE FAN1 RAD21 G6PC BRD4 PTCH2 MSH2 DHH EWSR1 SPRTN SDHC PTCH1 ALX3 CD79A TMEM67 INPP5E CCBE1 KRT6B BRCA2 ITK GINS1 HLA-DRB1 SNAI2 NBN PHOX2B BRAF CDH1 FANCE TYR GPC4 NF1 CD19 MVD AIP AR NBN TMEM107 BRIP1 ATRX BCHE MITF WRN BCR BCR NF2 SERPINA1 SDHB RABL3 PARN ANTXR2 TERT DPM1 IFIH1 GDF5 ZAP70 MEN1 TP53 GNAS BRCA2 TMC8 NODAL LETM1 VANGL1 TBXT BRCA1 FIBP FLT4 IL1B CCL2 FGFR3 SUFU MTAP ELANE CD19 HNF4A SAMD9 BUB1B KLHDC8B SLC26A2 FGFR3 FOXP1 PUF60 RUNX1 PTCH2 TRNK FLT4 TYROBP MPL KRAS RAD54L PIK3CA FAH CHEK2 CPLANE1 FAM20C CXCR4 DDR2 POU6F2 TMC6 SEC23B RET TRNP TFE3 TP53 NAB2 ANTXR1 MYSM1 SDHAF2 BTK TNFRSF10B DCLRE1C L2HGDH CDKN2A CYP11B2 BRCA2 SDHD TET2 TMEM216 BRAF PTCH2 TCF3 RPL11 NNT FLT3 BAX HAX1 IGF2 AKT1 FGFR3 MLH3 PLA2G2A TCF4 MLH3 NOTCH1 ERCC4 RRAS2 GPC4 DICER1 LZTS1 DOCK8 CASP10 GREM1 HPGD COL1A1 DCLRE1C IDH1 XRCC3 SUFU DNAJC21 PDGFRB TP53 NLRP1 WWOX TSC1 CTSC USP9X PDCD10 MEN1 ASCL1 RNF43 TNFRSF13C ESCO2 ZFPM2 AP2S1 PRCC HMBS ADA2 GANAB WT1 RNF43 HRAS KRAS SETD2 ATP6V1B2 FLT3 TJP2 BMPR1A PDGFB KIAA0753 PTEN STK4 NFKB1 BAP1 PMS1 MSR1 SLC26A2 RECQL4 MSH2 JAK2 ATRX FH RECQL4 FCN3 CD28 ASPSCR1 ADAR WHCR NOTCH3 GATA2 SMARCE1 CDKN2A RET ESCO2 EXT1 ERCC5 TET2 MBTPS2 NF1 OFD1 AGGF1 MVK KIT MUTYH HRAS KRIT1 FGFR1 TRIM28 CHEK2 CD79B GNAS BRCA2 KDSR BAX HACE1 MAP2K2 EDN3 ERCC2 CTNNB1 IL6 IGH PIK3CA MSH3 FZD2 SMPD1 SNAI2 PHOX2B SLC26A2 OFD1 PAX4 RB1 TRIP13 EWSR1 SCN9A PIK3R1 GBA EP300 PIK3CA HMMR KIT PDE6D ZSWIM6 SH3KBP1 SRP54 FUZ USP8 WT1 TERT MAFA FOXO1 GJB3 RAD51D POT1 SDHC PRKAR1A CREB1 SH2D1A WIPF1 WWOX PIK3CA NF2 HNF4A FAS RNASEH2A CD27 ATRX SPRED1 RPS14 FDPS RNR1 PALB2 NF1 MN1 TET2 GPC4 KDR SOX9 RAD51 MAX MYLK EP300 SHOX FOXE1 TCOF1 ESCO2 MYH11 HSPA9 MAD2L2 KRT9 CYP2D6 RFWD3 FANCE KRAS CCND1 LMO1 PTCH1 PORCN EDN3 PDGFRA DICER1 FANCA TERC CTBP1 SDHD ANTXR1 CXCR4 RAD50 BRCA2 MC1R MPL SLC22A18 MMP1 KRT16 F13A1 TSC2 ENG SETBP1 WT1 TET2 SDHC SMAD4 ZFHX3 GFI1 RNF113A STK11 KARS1 FOXE1 CDKN2B WT1 ERBB3 SMARCAD1 PDGFRL DMPK GTF2H5 NF2 CEBPA RPS28 PMS1 AKT1 PRDM16 NBN GCK SPINK1 ERBB2 JAK2 KIT DKC1 EXT1 JAK2 COL7A1 AXIN1 SLC22A18 NRAS ECM1 GNPTAB ABCA5 CDH1 NRAS ERCC6 VANGL1 RAD51C MYCN HBB TP53 SRY FANCI AKT1 MITF LEMD3 TARS1 TET2 NSD2 DAXX DYNC2LI1 OGG1 EXT1 TNFSF15 TERT ERCC6 DMRT3 SLC25A11 CTNNB1 VHL KLLN MLH3 EIF2AK4 GJB6 BARD1 OCRL GPR35 MYC DLST KRAS MSH3 RMRP PRKCD KLF6 NEUROD1 FANCG SLC17A9 BMPER FLCN SDHC SF3B1 STS GNA14 TERC MNX1 CAT TCF4 TUBB TRNQ BRCA2 IL12RB1 PDX1 CDKN2A SLC26A4 SDHC PPM1D NRAS PRKAR1A NRAS TAL1 KIF1B DNMT3A PDGFB MRAP ERCC3 CDC73 PRF1 RFWD3 PMVK RPL15 FGFR1 TP53 BICC1 HNF1A GATA1 RTEL1 RPS15A ERCC4 WRAP53 NR0B1 BCR FGFR2 SEC23A KRT17 NR5A1 VHL BLM BRAF ICOS POLD1 RPS27 FASLG CYSLTR2 PTEN PRKN THPO KIF7 NRAS TAL2 BRAF WDPCP DCC MSH6 NOP10 WNT10A PSAP ERCC2 CALR ACD SLX4 ACAN HABP2 GJB4 TET2 PHF21A ERCC3 MDH2 APC PALB2 RPL10 KRT17 PGM3 IL7R ARL6IP6 APC TCIRG1 NF1 SMAD4 PTPN3 PIK3CA ABCA5 FGFR2 TGFBR2 BRCA2 HNF1A RNASEH2C PAX6 IGH TTC37 DICER1 SRY GPC6 TOP2A KIT OFD1 PALB2 NRAS MC1R SDHD TFAP2A FGFR3 TNFRSF1B REST PTEN MST1R SCN4A BRCA2 CDKN2A FGFR2 ZIC2 EFL1 ECE1 NUP214 DDB2 GPC3 KCNQ1 PTEN HNF1B FN1 ASCC1 SPIB SRP72 PTEN FANCB KCNJ10 AKT1 KRAS KEAP1 INS DISP1 PTEN SASH1 CDKN1C ACTB TNFRSF13B MYH8 EDN1 IVNS1ABP NSUN2 TSC1 RAD51C MSH3 ATP7B RET PTPN12 STIM1 DHCR7 KRAS SFTPC BMPR1A XPC TMC8 KCNJ10 KDM6B STK11 KRAS GNAQ KRAS HFE HOXD13 B3GALT6 RPL5 KAT6B GATA2 MUC5B PIK3CA USP8 GDNF SMAD4 MVK RHBDF2 SSX2 CEP57 RAD51C NEK9 JAK2 PDGFB NRAS KRT1 PIK3CA MFN2 DOCK8 PTEN IL7 SDHC ATM AKT1 BRCA1 RELA GCDH PIK3CA IDH2 HRAS CTLA4 GPR143 ERCC2 GATA2 PTPN11 IGF2 SMAD4 NDUFAF6 CDH23 RPS7 RAD54B TP53 MUTYH GLI3 PTPN11 BRIP1 CDKN1B SF3B1 PTCH1 CIB1 ERCC3 PTPN11 TRPV3 GDNF IGLL1 PRKCD CTNNB1 PIK3CA PTPN11 SLCO2A1 FAH BRCA1 ETV6 BRCA2 EPCAM TP53 EXT1 BCL10 TRPS1 BMPR1A ATM MPL KRT17 MAX SLC12A3 ADA TERT UBE2T TSC2 TCTN3 MSH2 BDNF BTK SKI RPS20 NRAS RUNX1 DCC MSH2 RPS24 WT1 TRNF TFAP2A RPL35 RPS17 SDHA RARA CDC73 SBDS POLH BRAF LAMB3 RNF6 PIEZO2 KCNQ1OT1 CCM2 PHKA2 POU2AF1 TP53 TREM2 ABCC8 EXT2 ALK PHKG2 NUTM1 SLC26A4 PTCH1 MUTYH PALLD NBN FANCA SQSTM1 ELMO2 ACP5 TWIST1 TRIM37 RPL31 HFE RET DLC1 SDHB EP300 TREX1 HSPG2 ATP7A MSH6 C2CD3 CHRNG SRP54 TINF2 BUB1 PSENEN SMAD4 NF1 ERCC3 ARID1B RMRP WAS GATA2 MAPK1 BIN1 COL7A1 EDN3 PIK3CA IGF2 H19-ICR TUBB FH MLH1 TNFSF12 PIK3R1 RASA1 F5 SH2B3 CTNNB1 FOXI1 SUFU TLR2 SRSF2 CDKN1B GJC2 OPCML LEMD3 FIBP TRNS1 HNF1A VHL PTEN PRKAR1A MSH2 CYLD CTHRC1 COL7A1 DDB2 SDHC GJB2 LIG4 MDM2 LAMA3 CHEK2 MTOR CDON SMARCE1 TAF1 GNAQ TP53 RAD54L WWOX BMPR1A CCND1 GFI1 BCL10 PTEN CTNNB1 DHX37 SLX4 FGF8 XRCC4 TRIP13 CDC73 BIRC3 NOTCH3 DIS3L2 PKD2 KIF1B GNA11 ARMC5 CREBBP DIS3L2 HRAS LMX1B BAP1 BRCA2 POT1 ABCB11 AURKA RASA1 SMARCB1 ALX4 GPC3 MGAT2 PAX3 IGHM LMNA TCF4 GATA1 TRNK IDH1 LRP5 CALR FH RET SEC23B APC TET2 SETBP1 WT1 PMS2 POLR1C SIX3 EPHB2 RPL35A RET TINF2 CD28 CYP26C1 MNX1 ALX3 KIT CPOX GJB2 DLL1 MSTO1 RSPO1 TEK EXT2 ABCC6 COL2A1 GNAS FH FASLG BAP1 COL14A1 YY1 RAG2 RB1CC1 MAP2K1 RHOH STAR CREBBP RECQL4 EVC2 HBB ERBB2 ABL1 NDP SUFU NF2 MSH6 ATP7A TSC1 FAS SLC6A17 MS4A1 NQO2 FLCN EXTL3 SOS1 RNASEL NPM1 KIT GNAI3 TRNH RAG1 HRAS BUB1B IGF2 PLAG1 FANCD2 BCL2 NEK1 KIT ATP7A PIK3CA SMARCB1 PCGF2 LIG4 BCL6 NUP214 FLNA IRF5 ACVR1 GAS1 DYNC2H1 RSPRY1 TRAF7 RNASEH2B REST RPS29 TGIF1 TERT PIGA TP53 CDK4 GPR101 ACVRL1 SAMHD1 MSL3 MAPRE2 SLC45A2 CTNNB1 ADA KLF11 NKX2-1 GLI2 PKD1 MAP3K1 SRP54 TNFSF12 ND5 CRKL RASGRP1 BCL10 RPS26 GLI3 TRNL1 AR SDHA RB1 MLH1 MC2R TGFBR1 KIT CYP11B1 AXIN2 EGFR PIK3CA RECQL4 EXOC6B SMO SFTPA2 NRAS CDKN1B TP53 PIK3CA MSH6 ACTG2 POT1 SDHB RNF6 CALR KCNN3 C11ORF95 TSC2 CD96 SOS1 COL2A1 SMAD7 GLI1 FANCF MPL CDH1 BRCA2 BRAF ATR SDHA FLCN DICER1 IL1RN ICOS AIP RSPO1 DICER1 GCM2 XRCC2 DNASE1L3 PPP2R1B TGFBR2 MTM1 CDKN2C SIX1 MEN1 POU6F2 SRD5A3 STAT3 ERCC3 TG ASXL1 CDKN2B CYLD NHP2 CCDC22 TBC1D24 BLNK DIS3L2 SH2B3 MPLKIP AHCY PCNA EXT2 EXT2 MEN1 PARN WRAP53 TP53 HBB GABRD NUMA1 APC ZSWIM6 BRCA1 GJB2 KCNAB2 AIP USF3 RUNX1 H19 HDAC4 SDHD UROD PDGFRB CR2 HRAS CDH1 ERBB2 TNPO3 LPP SDHD IL2RG ATM BARD1 TREX1 POLE C2CD3 ERCC4 SLC25A13 PNP KRAS SRSF2 SDHB FGFR3 CASR CASP10 TET2 CTC1 ENPP1 SOX6 PIK3CA BMPR1A ERCC2 TERC CBL ADAMTS3 PIGL BCR SAMD9L NOD2 CBL TGFBR2 MALT1 SEMA4A ANTXR2 SLC37A4 TBX2 DHH STS SDHB TERT KRT16 DZIP1L RTEL1 SDHD CCND1 AKT1 FOXI1 CDK4 NSD1 MLH1 FLCN DLEC1 FGFRL1 MTMR14 GCGR TBX18 CREBBP MXI1 APC BCL10 COL11A2 TERT MC1R SCN10A RPS10 SMO BRCA2 KIT ATM PRKN MRE11 KIF1B KCNH1 VHL GPR101 GNAS PMS2 ACD WDPCP MAD1L1