SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Mutation E542K

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) With or Without Erlotinib (Tarceva, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer.

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating hormone-sensitive metastatic breast cancer. PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating hormone-sensitive patients with metastatic breast cancer.

NCT01013506 Breast Cancer Drug: IGF-1R inhibitor OSI-906 Drug: erlotinib hydrochloride Drug: goserelin Drug: letrozole
MeSH: Breast Neoplasms
HPO: Breast carcinoma Neoplasm of the breast

Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K ---

- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K ---

Primary Outcomes

Description: Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is > 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions

Measure: Time to progression

Time: from study entry to date of progressive disease

Secondary Outcomes

Description: The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death

Measure: Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib

Time: at 4 weeks

Description: Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

Measure: Response

Time: every 12 weeks to progression

Description: Levels of the protein C-peptide and the hormone IGF-1 in the blood

Measure: Circulating C-peptide, IGF-1

Time: At baseline and on day 1 of each 28-day cycle

Description: The levels of these biomarkers will be measured in breast tumor tissue and compared and contrasted with patient's time to progression and molecular classification (luminal A vs. luminal B)

Measure: Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

Description: Breast tumor tissue will be examined for mutations in these genes.

Measure: Mutation analysis of PI3K (E542K, E545K, H1047R)

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

2 A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving cisplatin and paclitaxel together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.

NCT01031446 Breast Cancer Drug: cisplatin Drug: everolimus Drug: paclitaxel Other: laboratory biomarker analysis
MeSH: Breast Neoplasms
HPO: Breast carcinoma Neoplasm of the breast

- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks. --- E542K ---

Primary Outcomes

Description: The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.

Measure: Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer

Time: at 8 weeks

Description: The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy

Measure: Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer

Time: at 8 weeks

Description: Patients who had not experienced disease progression and who were alive at 6 months after study entry

Measure: Patients With Progression-free Survival

Time: at 6 months

Secondary Outcomes

Description: Per Response Evaluation Criteria in Solid Tumor (RECIST) criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

Measure: Patients With Overall Response

Time: every 12 weeks

Description: Duration in months from date on-study to date patient exhibited progressive disease

Measure: Time to Progression

Time: Up to 64 weeks

Description: Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.

Measure: Time to Progression in Patients With Metastatic Basal-like Breast Cancer.

Time: Up to 64 weeks

3 An Open Label, Phase II Trial of BKM120 in Cancers With PIK3CA Activating Mutations

In people whos cancers have a PIK3CA mutation, this trial will be evaluating the drug BKM120 as a possible treatment. BKM120 works by blocking the phosphatidylinositol-3-kinase (PI3K)pathway, thereby inhibiting tumor growth and survival. The purpose of this study is to learn if the study drug BKM120 can shrink or slow the growth of your tumor. The safety of BKM120 will also be studied. Your physical state, symptoms, change in the size of your tumor, and laboratory findings obtained while you are on study will help the research team decide if BKM120 is safe and effective in patients with advanced cancers.

NCT01501604 Lung Cancer Breast Cancer Colorectal Cancer Cholangiocarcinoma Solid Tumors Drug: BKM120
MeSH: Cholangiocarcinoma
HPO: Cholangiocarcinoma

Inclusion Criteria: - At least 1 site of measurable disease - Life expectancy >/= 12 weeks - Adequate marrow and organ function - Diagnosis of lung cancer, breast cancer, colorectal cancer, cholangiocarcinoma, gastric cancer, pancreatic cancer, prostate cancer, uterine cancer, ovarian cancer, esophageal cancer, or head and neck cancer - Pathologically documented, definitively diagnosed, advanced solid tuor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy - Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L. --- E542K ---

The PIK3CA mutation must be documented in a CLIA approved laboratory Exclusion Criteria: - Prior treatment with a P13K inhibitor - Known hypersensitivity to BKM120 or its excipients - Untreated brain metastases - Acute or chronic liver, renal disease or pancreatitis - Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A - Diarrhea >/= CTCAE grade 2 - Any concurrent severe and/or uncontrolled medical condition - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Significant symptomatic deterioration of lung function - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKDM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breast-feeding - Known diagnosis of HIV infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Unable to swallow the medication in its prescribed form Inclusion Criteria: - At least 1 site of measurable disease - Life expectancy >/= 12 weeks - Adequate marrow and organ function - Diagnosis of lung cancer, breast cancer, colorectal cancer, cholangiocarcinoma, gastric cancer, pancreatic cancer, prostate cancer, uterine cancer, ovarian cancer, esophageal cancer, or head and neck cancer - Pathologically documented, definitively diagnosed, advanced solid tuor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy - Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L. --- P13K --- --- E542K ---

Primary Outcomes

Description: Objective Response Rate (CR or PR) by RECIST 1.1 criteria

Measure: Response Rate

Time: 2 years

Secondary Outcomes

Description: Clinical Benefit Rate (CR, PR, or SD) by RECIST 1.1 criteria

Measure: Clinical Benefit Rate

Time: 2 years

Description: Progression Free Survival (PFS)

Measure: Survival

Time: 2 years

Description: Determine if the presence of specific co-existing mutations may influence clinical benefit from BKM120

Measure: Clinical Benefit

Time: 2 years

4 Study to Evaluate the Safety and Efficacy of Sirolimus, in Subject With Refractory Solid Tumors

This study is a single arm, pilot study of sirolimus in patient with Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. sirolimus 1mg will be administered orally daily. To investigate the efficacy and safety of sirolimus in patient with Refractory solid tumor.

NCT02688881 Refractory Solid Tumors Drug: sirolimus
MeSH: Neoplasms
HPO: Neoplasm

- Patients must be >= 19 years of age - Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration( H1047R, E542K, E545K, PTEN LOSS) Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. --- H1047R --- --- E542K ---

Primary Outcomes

Measure: Progression Free survival

Time: 6 Weeks

Secondary Outcomes

Measure: Overall Response Rate

Time: 24 months

Measure: Time to progression

Time: 24 months

Measure: Overall survival

Time: 24 months

Measure: Number of subjects with Adverse Events as a measure of safety

Time: 24 months

5 A Phase II Evaluation of Copanlisib (BAY 80-6946), a Selective Inhibitor of PI3KCA, in Patients With Persistent or Recurrent Endometrial Carcinoma Harboring PIK3CA Hotspot Mutations

This phase II trial studies how well copanlisib works in treating patients with endometrial cancer that has not decreased or disappeared, and the cancer may still be in the body despite treatment (persistent) or has come back (recurrent). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02728258 Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Drug: Copanlisib Other: Laboratory Biomarker Analysis
MeSH: Carcinoma Adenocarcinoma Carcinoma, Endometrioid Cystadenocarcinoma, Serous
HPO: Carcinoma

Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.. Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Carcinoma Adenocarcinoma Carcinoma, Endometrioid Cystadenocarcinoma, Serous PRIMARY OBJECTIVES: I. To assess the activity of copanlisib (BAY 80-6946) in patients with persistent or recurrent endometrial carcinoma harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) hotspot mutations with the frequency of objective response. --- R88Q --- --- N345K --- --- C420R --- --- E542K ---

Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.. Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Carcinoma Adenocarcinoma Carcinoma, Endometrioid Cystadenocarcinoma, Serous PRIMARY OBJECTIVES: I. To assess the activity of copanlisib (BAY 80-6946) in patients with persistent or recurrent endometrial carcinoma harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) hotspot mutations with the frequency of objective response. --- R88Q --- --- N345K --- --- C420R --- --- E542K --- --- E545A --- --- E545D --- --- E545G --- --- E545K --- --- Q546E --- --- Q546K --- --- Q546L --- --- Q546R --- --- M1043I --- --- H1047L --- --- H1047R --- --- H1047Y --- --- G1049R --- --- R88Q --- --- N345K --- --- C420R --- --- E542K ---

Primary Outcomes

Description: Confirmed complete and partial tumor response by RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Measure: Frequency of Objective Response Defined by RECIST 1.1 Criteria

Time: approximate study duration 1 year 9 months

Secondary Outcomes

Description: Percentage of participants who are progression free at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Measure: Percentage of Participants Alive and Progression-free at 6 Months

Time: Up to 6 months from enrollment

Description: The median progression-free survival time

Measure: Median Progression-Free Survival Using RECIST 1.1 Criteria

Time: September 16,2016 to April 4,2019, approximate duration of 2 years, 7 months

Description: Median time of overall survival

Measure: Median Overall Survival

Time: September 16,2016 to April 4,2019, approximate duration of 2 years, 7 months

Description: Maximum grade of physician assessed adverse events reported during treatment

Measure: The Frequency and Severity of CTCAE v4 Graded Adverse Events

Time: Study Start: September 16, 2016, Primary Completion: June 30, 2018, approximate study duration 1 year 9 months

Other Outcomes

Description: Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.

Measure: Mutation Subtypes and Clinical Outcomes

Time: Up to 5 years


HPO Nodes


Breast carcinoma
Genes 95
TP53 PPM1D CTNNB1 TP53 COL14A1 AKT1 AKT1 OPCML MDM2 BRCA1 SLC22A18 POLE BRCA2 BRCA1 SDHC NTHL1 PTEN XRCC3 MSH6 IDH1 RAD51C RAD51C CASP8 RB1CC1 PIK3CA PALLD KRAS PIK3CA CHEK2 BRIP1 MRE11 NTHL1 ATM TP53 RAD51D STK11 PRKN ESR1 PIK3CA KLLN MSH2 SDHD KRAS SEC23B HMMR PTEN POLD1 PIK3CA IDH2 BRCA1 PALB2 BRIP1 TP53 RAD51 RNF43 BARD1 BARD1 AAGAB AKT1 SMAD4 RAD50 STK11 CHEK2 RAD54L NBN CDKN2A SEC23B CDH1 WRN NQO2 PALB2 ATR PALB2 TWIST1 SDHB MSH2 BRCA2 BRCA1 RAD51 CHEK2 MLH1 BRCA1 FGFR2 TP53 PHB BRCA2 CDH1 PTEN BRCA2 CHEK2 CDKN2A APC MLH1 AKT1 APC
Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT
Cholangiocarcinoma
Genes 3
MST1 TCF4 GPR35
Neoplasm
Genes 1473
GPC3 LETM1 LZTS1 REST MPL ARID1B RPL18 MGMT GLI3 BIRC3 ZSWIM6 TRNS2 ETV6 HNF1B KIT BRCA1 SUFU PLAG1 SOX9 TP63 CTSC RASA1 ATRX TRIM37 SUFU BTK CYP11B1 NOTCH3 EPCAM PORCN PIGL AR TET2 FH TGIF1 HMBS ATRX TREX1 SMAD4 KRT17 FGFR1 WDPCP SF3B1 GPR101 KIT GLI1 SLC25A11 XRCC4 SDHD PRKCD RNF43 SDHB BAP1 EGFR PIGA NF1 ASCL1 MPL RET C2CD3 GDNF NR5A1 DICER1 TNFRSF4 CASP10 TERC FGF8 PSAP CIB1 SLC22A18 PTCH2 ENPP1 CDKN2C SLC25A11 GPR101 KIT AXIN2 TREX1 DYNC2LI1 ERCC4 RPS14 COMP TINF2 FOXE1 DHCR24 RPS7 TYROBP HOXD13 ERBB2 BLK EYA1 ZFPM2 ERCC6 NLRP1 STAC3 ERCC5 NUTM1 MEN1 WT1 BCL10 GNPTAB KRAS TP53 KDR PUF60 TRNF FCN3 SDHC KCNH1 MSTO1 EP300 BUB1B GNA11 KCNE3 DOCK8 SEMA3C ACD GLI2 SMPD1 SUFU NF1 PTCH2 ACAN DCC WT1 CTSA KIF11 BCR SRGAP1 KIT PTEN LEMD3 MLLT10 SCN4A BRCA2 BMPR1A NOTCH3 SEC23A CDKN1C BARD1 SPIB RSPO1 MC2R CALR ATP6V1B2 NBN RAD54L MST1 SUFU MYCN TMEM127 SRD5A3 IGF2 CD28 RUNX1 OGG1 HAX1 SDHC CTNNB1 MST1R SDHA IGF2 KCNJ10 IL12RB1 MEN1 RAD51 TFE3 ND5 MMEL1 MVK APC FLI1 RNF6 NF1 BRCA2 SUFU GPC6 NR4A3 TTC37 KIT NRTN BLNK IGH SPRED1 TXNRD2 IGF2R FOXP1 BUB1B SOS1 LRP5 GJB2 DNMT3A PMS2 PRKN RET MSH6 ACVRL1 MPLKIP ERCC2 AIP GNAS TAL1 NNT RECQL4 PMS1 DLL1 EIF2AK4 STAT6 MNX1 SDHB KRAS MEN1 MN1 SH2B3 EFL1 VHL KLLN RMRP RUNX1 SIX3 GDNF FANCD2 EXT1 CDH23 BRD4 DLEC1 NODAL CARMIL2 SDHB MSH2 HMBS SMAD4 SRP72 NRAS DOCK8 SPRTN BRCA1 MAP2K1 KRT14 LETM1 TERT MAP2K2 HRAS WHCR WT1 IDH1 TMEM107 SCN10A GJB3 SDHD KRAS GATA1 RPS20 GJB2 SLX4 USP8 PRKAR1A CR2 JAK2 HFE MPL POT1 BRCA2 GNAI3 SDHB ALK OCA2 TP53 GPC4 ACTG2 CTNNB1 HSPG2 AR FGFR1 STK4 MET TMC8 MRAP MSH6 CCBE1 EWSR1 LMO1 EDN3 LEMD3 PGM3 FGFR3 CASP8 RB1CC1 SCN9A FANCL TG SDHD COX3 IGF2 COL11A2 AGGF1 GPR101 PRKN PLCB4 SDHD NF1 GTF2E2 MAP2K1 ESCO2 CDC73 WRAP53 TET2 PDGFRB RNASEH2A RAD21 HNF1A TGFBR2 POLD1 COX2 TNFRSF10B MINPP1 DNAJC21 FAS EXT1 SLC26A2 APC SDHAF2 TINF2 LIG4 POLR1D WWOX TMC6 RPS19 ERCC2 SASH1 MC1R MVD SEC23B CYP2A6 GPC3 KIT HRAS RAD54L SDHA GDNF NKX2-1 GFI1 ALX3 STAT3 MYH11 DYNC2LI1 FGFR2 TCOF1 PTEN MAFA PIK3R1 SLC25A13 HRAS VHL COL7A1 GNAS FGFR2 PIK3CA GPC4 DICER1 ERCC3 PIK3CA RAD51C RB1 RMRP MLH3 ATM COL7A1 LIG4 NF1 VAMP7 RPL35A RB1 SETD2 BCL10 LPP NRAS KRAS ABCA5 ERCC2 PDE6D KCNQ1OT1 MS4A1 SLC22A18 APC LIG4 JAK2 FANCD2 GAS1 STAG3 NRAS PALLD SLC22A18 RFWD3 PPP2R1B APC PTPN11 PTEN WIPF1 PIK3CA NOP10 IL7 UROD TNFRSF1B TP53 REST SLC37A4 NHP2 CXCR4 KIT CYSLTR2 FZD2 ALX4 BMPR1A SRY TRNQ SDHD PIGL CCM2 FIBP FANCI GJB4 SPINK1 RPL10 NSD2 MAP3K1 RET CDK4 HSPA9 TET2 GFI1B MAD2L2 DCC AP2S1 SMAD7 BRCA2 TRNK ERCC3 BRCA1 ELANE SFTPC PTH1R COL1A1 FUZ OFD1 RET FLT4 PRKAR1A SBDS RPL26 SMARCE1 SMARCAD1 MSH2 BCR GPR35 INTU FANCA STAT1 ANTXR2 FGFRL1 TUBB BRAF SLX4 CASP10 TERT RAD21 MTOR TRIP13 MYD88 DPM1 RSPO1 PTPN11 CTNNB1 AIP PTEN VANGL1 CYP2D6 RPS10 GCK KRT16 DNAJC21 BCL2 AKT1 KRAS KLF6 NOTCH1 FLNA MAX NF2 PALB2 TP53 PSENEN RNF6 TSC1 HNF1B TP53 RFWD3 SDHD PERP TP53 DIS3L2 B3GALT6 STS PDGFB SMARCB1 BRAF BRIP1 CBFB BUB1 BLM INHBA CALR NBN MLH3 TAF1 MLF1 PIK3CA MSH2 CTLA4 ND6 PALB2 WT1 PTCH1 POLE ADA MC1R FLT4 ATP7A MLH3 SMO TRNF NRAS LMNA DLST TRNL1 MTAP TP53 ZAP70 SDHB CHEK2 PALB2 FLT4 CDK4 NBN MSR1 CC2D2A TNPO3 ECE1 RPS15A NAGS TMEM67 HNF1A PIK3CA ATP7A AKT1 NRAS SDHAF2 CXCR4 TSC2 NF2 EPHB2 WDPCP OFD1 BUB1 FLT3 APC SMARCA4 CDKN2A RPS29 MCM4 PDGFRA ESCO2 CTC1 ESR1 SDHB MSH6 APC HABP2 GNAQ KIF1B SH3GL1 CD70 MPL IGH ZIC2 GCM2 VEGFC HRAS CTNNB1 KCNH1 LRRC8A BRAF FAS ICOS NSD1 RNF43 AKT1 BIN1 DLC1 SH2B3 RARA WNT10A CARD14 SDHC EXOC6B ESCO2 POLR1C G6PC MSH6 KRT1 PDX1 TNFRSF13C ERCC3 EVC SNAI2 CD79A BRCA1 RNASEH2B CCND1 TP53 RPS19 H19 H19 BRCA2 TFAP2A ARMC5 FASLG FGFR3 APC F5 EDN1 MAP3K8 AIP APC AKT1 TERC CCND1 CEL MYC TP53 GPC4 ERCC5 HNF1A POLE DAXX NUP214 TRIP13 AKT1 TET2 CDC73 ND1 MUTYH PIK3R1 TERT CEBPA EXT2 OCRL DIS3L2 ADAR TGFBR2 BRCA2 MRE11 SOS1 HNF4A FAH TMEM127 WT1 AXIN2 TCF4 EDN3 PTPN3 KRAS SEMA4A PIK3CA XPA MFN2 TINF2 PIK3CA APPL1 RUNX1 GNPTAB FGFR3 NRAS PDCD10 RAG2 PTEN CTNNB1 SOX2 BMPR1A HBB TERT USP9X NFKB1 FANCC PRF1 WRN SRY SRSF2 PMS2 RHBDF2 PHOX2B RPS17 PAX3 RECQL4 KIF1B SQSTM1 RB1 EXT1 XPC CYLD TOP2A MYD88 CDKN1B TET2 GJB2 PTEN UBE2T RTEL1 PTCH1 KLHDC8B GATA1 POLH JAK2 RHOH FLCN DCLRE1C MTMR14 GTF2H5 PTEN SBDS TBC1D24 PAX7 AR TP53 ASPSCR1 MTM1 RECQL4 ERCC2 TGFBR2 ERCC4 JAK2 SF3B1 CDKN2B XPC GATA4 KIT POU2AF1 BRCA2 GREM1 CDON NTHL1 DICER1 GINS1 ATM RAD51D SHOX EXT1 RASGRP1 WT1 GATA2 NF2 ERCC4 TUBB MBTPS2 DHCR7 MYLK KCNN3 TCTN3 TMEM216 TMEM231 KRT1 CTNNB1 MPL PDGFRB FANCG RPGRIP1L KEAP1 DICER1 WT1 BAP1 FOXI1 ERCC4 CDKN2A FGFR3 KDSR CBL HRAS BMPR1A DISP1 RELA MAP3K1 PARN BCR ENG COL7A1 LMOD1 KRAS PAX6 SNAI2 GLI3 FANCF FOXO1 RPL15 TBX18 TRPV3 PIK3CA NRAS CDH1 GNAS SMARCB1 KLF11 ADA2 EDN3 POU6F2 CDH1 GNAS IL1B SMAD4 H19-ICR SDHB STK11 NF2 TRIM28 SEC23A SLCO2A1 BRCA2 BRAF DNMT3A MDM2 BMP2 BRCA2 DHH NRAS POU6F2 CTBP1 PTCH2 FLCN CALR BAP1 LIG4 HRAS REST BRAF SAMD9 NDP TYR KRT17 MUC5B PRSS1 MEN1 NPM1 ITK MSH2 CYLD TAL2 SRP54 IFIH1 HMMR TCTN3 ND5 JAK2 FAM20C RET NEK9 DMRT3 KRAS MINPP1 SH3KBP1 THPO FAH KRT5 JAK2 PHKG2 TSC1 TNFRSF13C MEN1 FH RPL31 FANCG PIK3CA IL2RG DNAJC21 VANGL2 MYO1H ALX1 CDKN2A AIP H19 NRAS TWIST1 PTEN TRNK TRPS1 RPS26 MAPRE2 RPS27 TCF3 KRT17 ERCC6 DHH MMP1 FGFR1 SEMA3D PTCH1 ABL1 CDKN2A SKI APC WWOX ZSWIM6 NF2 WNT10A KRAS GPC3 REST GJB6 HRAS VHL CTNNB1 TGFBR1 IL6 TDGF1 RPL11 IL1RN BRCA1 MGAT2 POT1 ASCC1 XPA TBX2 FLCN HFE NTHL1 SMARCB1 DVL3 TRNH IDH1 FANCA LAMB3 CD79B RAD51C PRDM16 PHOX2B GNAQ CCL2 PDGFRA CREB1 SRP54 PIEZO2 TRNL1 GBA GNAS WNT5A PIK3CA STS FANCB KRAS MAGT1 RAD51 IDH1 TNFRSF13B TREM2 GABRD BCL10 SKIV2L POLD1 KRIT1 KRAS ARSA SMAD4 RAD51 TP53 DIS3L2 KIAA0753 PRLR CD96 LZTR1 WRN GATA2 EDNRB MUTYH ATM CHIC2 TP53 CYLD PAX4 SLC26A4 RTEL1 VHL NEK1 TRNS1 GCM2 TYR ATP7B CTHRC1 BRAF ASXL1 OFD1 MLH1 CDKN1A PHOX2B XRCC2 CD19 RB1 FOXC2 TRIM28 EWSR1 TERT GNA11 F13B CDKN2A KARS1 BCL10 TP53 WT1 CDKN2A FDPS KIT COX1 COL14A1 VHL WT1 TERT SMAD4 STAR NUMA1 RPL5 PDGFB PCGF2 CFTR KCNQ1OT1 KIT GJA1 GNAQ CD27 FANCC IDH2 EVC2 BRCA2 TCF4 KRAS PIK3CA CDC73 ACVR1 BRIP1 TRNW PRCC GCGR CDKN1B STK11 SCN11A TGFBR2 AXIN2 ERBB2 RPL35 APC TSC2 IL12A SSX2 TET2 KIF1B DICER1 TRNP BTK CCDC22 PDGFRA ALX3 ADAMTS3 CD81 RET DKC1 GLI3 FGF3 SMAD4 STK11 ERCC6 WT1 ELANE C11ORF95 SAMD9L SLC45A2 NQO2 PTPN11 ATR PDGFRL TNFSF12 BRCA2 ADA BUB1B FASLG GDF5 KRAS CPLANE1 CREBBP CDC73 CLCNKB GATA2 CTRC SDHA ACTB APC BMPER SPINK1 APC2 MC1R FOXI1 DYNC2H1 KIT PPM1D SDHC NSD1 SDHC DDX41 ANTXR1 CASP8 F13A1 SUFU INS NUP214 ANTXR2 KIF7 NFKB2 ABCC8 TARS1 ERCC3 TCIRG1 ND4 ERCC2 GNAS TERT WASHC5 SLC49A4 RERE CALR MSH3 PHOX2B SLC25A13 BMPR1B CYLD SIX6 ASCL1 IDH2 FAN1 CHRNG CBL NEUROD1 MSH3 THPO VANGL1 CDKN2B TAF15 PTCH2 HMGA2 MSH6 CHEK2 FN1 GATA2 IRF1 KRAS BMPR1A NPM1 ERCC3 CDH1 ALK DNM2 ERBB3 PTPN11 DLST MUTYH PARN GFI1 NBN FGFR3 CHEK2 EP300 RNF113A TNFSF15 TEK TERF2IP ICOS COL18A1 TNFSF12 BRAF CHEK2 IFNG TMC6 USB1 KDM6B GJC2 SLC26A2 MDH2 TP53 ENG MLH1 KRT6B MNX1 PDGFB TRNH POLE CASP10 HPGD TET2 RB1 PHOX2B JAG1 GNB1 ACD TNFRSF13B MYC BRAF TSC1 SAMD9L BCL10 H19 POT1 USP8 IGF2 OFD1 CYP11B2 KCNQ1 CDH1 LMX1B TET2 ANTXR1 JAK2 SMARCB1 ELMO2 PTCH1 SIX1 L2HGDH WRAP53 BUB3 AXIN1 RET KCNJ11 ABL1 FANCE RAD54B FANCM TSC2 MAX IGHM TSC1 HACE1 CASR RNF139 MITF RAF1 WT1 TCTN3 POLH LIG4 TP53 KRT10 AAGAB SRY RAD50 TNFRSF1B TRNQ DNASE1L3 FAM149B1 KRT9 VHL FLCN TBXT SLC37A4 DKC1 PNP DDB2 SETBP1 ECM1 MSH2 CR2 COL2A1 COL7A1 MLH1 FH SFTPA2 PIK3CA FOXH1 MET HNF4A H19 KAT6B GPR143 PHB PMS1 ATP7A FAT4 TJP2 TFAP2A GDF2 AHCY TSC2 CD19 TRNS1 BDNF TRIP13 AKT1 FGFR2 RAG1 BRCA1 SDHC MLH1 XRCC3 NSD2 LMNA SDHC TERC EXT2 PIK3CA MSH3 SDHD SRC CHEK2 C1S ABCA5 HBB RYR1 FGFR2 CDC73 KIT FANCE RET LYST KCNJ10 BCHE HDAC4 INPP5E CRKL PHOX2B BAP1 CPLX1 PDGFRB ARL6IP6 RNASEL SETBP1 CTLA4 PALB2 DCLRE1C NSUN2 XIAP TRNS2 BMPR1A IL7R BCL6 COL4A5 PIK3CA NOD2 PRKAR1A NELFA IL2RG MYH8 RHBDF2 IGLL1 PIK3CA SERPINA1 FOXE1 ARHGAP26 TCF4 MITF ABCB11 ERBB2 GNA14 SLC26A2 NSD1 SH2B3 STK11 PTCH1 GDNF RPL27 DHCR7 WAS CIB1 SHH CACNA1S LIN28B SF3B1 ATM PRKCD RPS24 LAMA3 ATRX CASP8 AKT1 OPCML HFE SH2D1A ING1 CCND1 SLC12A3 HABP2 H19 LAMC2 RAD51C NAB2 NRAS MAPK1 CPLANE1 CYP26C1 CDKN1B CHD7 IGH MYF6 BLM ASXL1 FH NEK1 HLA-DRB1 SLC26A4 RPS14 SHOX RNASEH2C SMARCD2 GATA2 CDH23 WT1 EPCAM NR0B1 KLLN DVL1 SEC23B GPC3 SLC17A9 BRCA1 SRP54 DKC1 RECQL4 CD28 PTPN11 HRAS NBEAL2 BARD1 MLH1 DDB2 PMS2 IRF1 ABCC6 EXT2 ASXL1 TSR2 PTEN MALT1 PTEN BCR PALB2 BRIP1 SSX1 PHKA2 FGFR2 SDHB FERMT1 KCNAB2 FLT3 PMVK MSTO1 CEP57 MMP1 PICALM IRF5 TP53 PTPRJ RNR1 WWOX PLCD1 RPS28 FGFR3 COL2A1 IKBKG TERT RASA1 SAMHD1 PHF21A