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Report for Clinical Trial NCT03551626

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)

This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes. Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm. This study consists of two Periods for Enrolled subjects: - Treatment Period - subjects will receive up to 12 months of treatment. - Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.

NCT03551626 Malignant Melanoma
MeSH:Melanoma Fever
HPO:Cutaneous melanoma Fever Melanoma

2 Interventions

Name: Dabrafenib

Description: Supplied as dabrafenib 50 mg, 75 mg Capsules for oral use
Type: Drug
Group Labels: 1

Dabrafenib and trametinib combination therapy

Name: Trametinib

Description: supplied as trametinib 0.5mg, 2.0mg tablets for oral use
Type: Drug
Group Labels: 1

Dabrafenib and trametinib combination therapy


Primary Outcomes

Description: The composite rate of grade 3/4 pyrexia, ospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated subjects

Measure: Change from baseline in composite rate of pyrexia related events

Time: Baseline up to 12 months

Secondary Outcomes

Description: RFS is defined as the time from the date of first dose of the study medication to the date of disease recurrence or death due to any cause.

Measure: Relapse free survival (RFS) from the first dose to disease recurrence or death from any cause

Time: Baseline up to approximately 24 months

Description: OS is defined as the time from date of the first dose of study medication to date of death due to any cause.

Measure: Overall Survival (OS) from the first dose to date of death due to any cause

Time: Baseline up to approximately 24 months

Description: Percentage of patients who experienced pyrexia and required intervention

Measure: Percentage of patients who require management of pyrexia

Time: Baseline up to 12 months

Description: Participants who permanently discontinued treatment due to any Adverse event during treatment

Measure: The percentage of participants who permanently discontinued treatment due to any Adverse event

Time: Baseline up to 12 months

Description: QoL assessed using Function Assessment Cancer Therapy-melanoma (FACT-M) assessment tool. This includes the FACT-Melanoma subscale (FACT-M MS) questionnaire -specific subscale consists of 16 questions for Melanoma Subscale (MS) and 8 questions for Melanoma Surgery Scale (MSS).Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life.

Measure: Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M MS)

Time: Baseline up to 24 months

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 V600E

Higher scores represent a better quality of life.. Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---

Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ - History or current evidence of cardiovascular risk - A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---



HPO Nodes


HPO:
HP:0001945: Fever
Genes 344
TRNF MEFV SCNN1B TNFAIP3 LPIN2 IL2RG CD247 WT1 TH TLR3 SCNN1A IL2RG NLRP3 TET2 ERCC4 SPINK1 HLA-DRB1 MLX LIPA NGLY1 TCF4 PTS ATP1A3 LPIN2 HAVCR2 KLRC4 DCLRE1C NPM1 NOTCH3 KIF1B H19 NOD2 SPINK1 IL12A CTRC TRNL1 LPIN1 RYR1 LRRC8A PRKAR1A BCL10 CRLF1 GAA NKX2-1 NLRP3 CHD7 FIP1L1 ND4 SLC29A3 PTPN3 LACC1 KRT8 CASK IRAK1 SCYL1 RNASEH2B SPTB MST1 PML MALT1 AQP2 TBL1XR1 IL12A-AS1 ERAP1 SH3KBP1 CD79B LBR SRP54 SLC12A1 IL7R TP53 SPTA1 SLCO1B1 EIF2B4 TRNK FOXP1 IL7R SLC19A3 TRIM28 UNC93B1 ND1 NLRP3 SCNN1G ELP1 RYR1 RANBP2 IFIH1 NAB2 NGF JAK2 WT1 COX2 NCF2 MVK CTRC BCL2 STAT6 ANK1 KRT18 IRF8 ELANE COG6 CYP11B2 CD79A NOD2 CFH RNASEH2A QDPR ADAMTS13 BCR CACNA1A ERCC3 IGH BLNK PSMB9 ND3 HMGCL RMRP TCF3 EIF2B2 SLC29A3 BRCA2 GYPC IGH CACNA1S HLA-B TRNQ CACNA1S HLA-DPB1 SPTB ERCC2 ADAR ADA NCF4 CPT2 TMEM165 MEFV POMP C4A ABL1 STX11 CD27 UBAC2 GALC CALR PTPN22 IRF8 ZFHX2 NTRK1 NLRP3 HLA-DRB1 TSC2 TRNS1 NCF1 TRIP13 TP53 IL23R F5 STAT3 STAT3 RAG2 NLRC4 PRSS1 IBA57 CHEK2 TSC1 ELANE ADA2 BTK EPB41 C1R GFI1 BCAP31 TRNL1 COL1A1 FBP1 POU6F2 TET2 SLC4A1 PRNP PIK3R1 GLA LIFR SLC12A3 CFTR EIF2B3 PRKAR1A AVPR2 DDB2 CYTB TLR4 BIRC3 PEX6 HAVCR2 IRF2BP2 HLA-DPA1 ACAT1 ND1 SPTA1 STAT4 TRAF3 DIS3L2 IL10 EIF2B5 GCH1 ATM TNFRSF1A IGH RB1 RAG1 ND6 XIAP HBB EIF2B1 BCOR ND2 MPL KCNJ1 ND5 TRIM28 STAT4 PSMB8 HLA-B WAS EPB42 NLRP12 AK2 TRNW COX3 HTR1A POLR3A LIFR HMGCL P4HTM TNFRSF1A RNASEH2C STIM1 MYD88 BTNL2 SH2B3 TRNH COX1 CYBA PSMB4 IKZF1 KLHL7 GATA2 JAK2 NLRP1 REST CFHR1 ZBTB16 CALR NLRC4 NUMA1 LIG4 GPR35 AVPR2 ND5 ATP6 RAG1 ND4 SLC11A1 BCL6 TREX1 XPA TRNS2 IL36RN PTPN22 ALPL STAT5B C1QA LYST SAMHD1 ERCC5 RAB27A RAG2 CFHR3 PMM2 AVP XPC NLRP3 NLRP3 CYBB JAK2 TCIRG1 CYP11B2 RYR1 MPL ATP1A2 MEFV IL12B FAS CCR1 MYD88 PSTPIP1 RUNX1 CD3E ABCC2 HLA-DRB1 ORAI1 SPP1 TBK1 TRNV AQP2 COL1A1 CYP21A2 PMP22 TICAM1 HLA-DRB1 EDA STING1 RNF168 GPC3 NABP1 ATP13A2 TREX1 DST PRSS2 UNC13D IFNGR1 CD3D WIPF1 NLRP3 CFTR IGHM CYBC1 STXBP2 ND6 CTLA4 PRTN3 RARA IGLL1 MEFV IL6 NLRC4 CCND1 HLA-B NLRC4 PRSS1 SLCO1B3 G6PD MIF TRNW
SNP 0