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

• Status: Completed
• Trial end date: 2019-04-12
• Target enrollment: 0
• Participant gender: All

Summary

Dose escalation part: to determine the highest dose of alpelisib administered on a daily basis when given in combination with daily everolimus or in combination with daily everolimus and exemestane.

Dose expansion part: To describe safety and tolerability of the alpelisib and everolimus or alpelisib, everolimus and exemestane combinations.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Everolimus; Exemestane; Sirolimus

Criteria

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