Study of Safety and Efficacy of Alpelisib With Everolimus or Alpelisib With Everolimus and Exemestane in Advanced Breast Cancer Patients, Renal Cell Cancer and Pancreatic Tumors

This is an interventional treatment trial for Neoplasms focused on measuring Solid tumors, renal cell carcinoma (RCC), pancreatic neuroendocrine tumors, breast cancer, PI3K inhibitor, BYL719, alpelisib, everolimus, exemestane Read More

Inclusion Criteria For entire trial:

• Adult > or = 18 years old
• has signed the Informed Consent Form
• has tumor tissue available for the analysis as described in the protocol
• has an Eastern Cooperative Oncology Group performance status ≤2
• has adequate bone marrow and organ function as defined in the protocol
• is able to swallow and retain oral medication
• has either measurable or non-measurable disease as per RECIST 1.1.

Inclusion Criteria for the BYL719+ Everolimus combination - escalation phase - all above plus has a histologically/cytologically confirmed metastatic and/or recurrent solid tumors for whom no standard therapy exists.

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, renal cell carcinoma cohort - all of above first 7 criteria plus has an histologically/cytologically confirmed Renal Cell Cancer as detailed in the protocol

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, pancreatic NeuroEndocrine Tumor cohort

- all of above first 7 criteria plus has an histologically/cytologically confirmed pancreatic NeuroEndocrine Tumor as detailed in the protocol

Inclusion Criteria for the BYL719+ Everolimus combination - expansion phase, mTOR inhibitor-pretreated patients' cohort - all of above first 7 criteria plus has a histologically and/or cytologically confirmed solid malignancy as described in the protocol

Inclusion Criteria for the breast cancer cohorts in escalation and expansion phases, - all of above first 7 criteria plus is post-menopausal and has a histologically and/or cytologically confirmed diagnosis of breast cancer as described in the protocol

Specific Inclusion Criteria at the time of cross-over (breast cancer, expansion phase),

- Patient randomized to the alpelisib and exemestane combination who has a radiologically documented progressive disease as detailed in the protocol

Exclusion Criteria:

• Patient has received previous treatment with a PI3K and/or AKT and/or mTOR inhibitor (mTOR inhibitor is allowed in expansion cohorts where patients should have areceived a prior mTOR inhibitor)
• Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs
• Patient with primary central nervous system (CNS) tumor or CNS tumor involvement as detailed in the protocol
• Patient with diabetes mellitus, or documented steroid-induced diabetes mellitus
• Patient has a history of another malignancy within 2 years prior to starting study treatment as described in the protocol
• Patient who has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy as detailed in the protocol
• Patient who has had systemic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment
• Patient who has received radiotherapy ≤ 4 weeks prior to starting study drugs, with exception of palliative radiotherapy (≤ 2 weeks prior to starting study drugs), who has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated
• Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
• Patient has a clinically significant cardiac disease or impaired cardiac function or any severe and/or uncontrolled medical conditions as detailed in the protocol
• Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
• Patient who has participated in a prior investigational study within 30 days prior to enrollment as described in the protocol
• Patient who is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP34A or CYP2C8 as described in the protocol. Switching to a different medication prior to start of treatment is allowed
• Patient with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral alpelisib, everolimus, exemestane
• Patient with known positive serology for human immunodeficiency virus
• Patients who have received live attenuated vaccines within 1 week of start of study drug and during the study as specified in the protocol.
• Pregnant or nursing (lactating) woman as detailed in the protocol.
• Patient who does not apply highly effective contraception during the study and through the duration as defined in the protocol
• Patients in the mTOR inhibitor-pretreated cohorts: all of above first 19 criteria plus have discontinued prior mTOR inhibitor therapy due to non-tolerable toxicity