NCT02077933

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

A Phase Ib Dose-finding Study of BYL719 Plus Everolimus and BYL719 Plus Everolimus Plus Exemestane in Patients With Advanced Solid Tumors, With Dose-expansion Cohorts in Renal Cell Cancer (RCC), Pancreatic Neuroendocrine Tumors (pNETs), and Advanced Breast Cancer (BC) Patients.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The main purpose of the study was to determine the maximum tolerated dose/recommended dose for expansion (MTD/RDE) of alpelisib in combination with everolimus, and of alpelisib in combination with everolimus and exemestane, and additionally to describe safety, preliminary efficacy and the magnitude of the alpelisib-everolimus interaction. The study was conducted in patients with metastatic and/or recurrent solid tumors including renal cell carcinoma (RCC), pancreatic neuroendocrine tumor (pNET), and advanced solid tumors previously treated with an mTOR inhibitor, to evaluate everolimus and alpelisib, and in postmenopausal females with HR-positive HER2-negative advanced breast cancer to evaluate everolimus, alpelisib and exemestane. This was a Phase Ib, open-label, multi-center, dose-finding study. The initial dose level of alpelisib was 300 mg every day (qd) and everolimus was initially administered at 2.5 mg qd. The dose-finding study (escalation phase) was followed by an expansion phase where safety and preliminary efficacy of the doublet (alpelisib and everolimus) as well as of the triplet (alpelisib, everolimus and exemestane) were assessed in selected subject populations. Alpelisib, everolimus and exemestane were administered orally once daily on a continuous dosing schedule and dosed on a flat-fixed dose and not by body weight or body surface area, starting on Day 1 in a 28-day cycle. In the doublet escalation phase, alpelisib was administered at 300 mg or 250 mg in combination with 2.5 mg everolimus. In the triplet escalation phase, alpelisib was administered at 200 mg in combination with 2.5 mg everolimus and 25 mg exemestane. In the doublet expansion phase, alpelisib was administered at 250 mg in combination with 2.5 mg everolimus. In the breast cancer expansion phase, alpelisib was administered at 200 mg in combination with 2.5 mg everolimus and 25 mg exemestane or alpelisib was administered at 250 mg in combination with 25 mg exemestane. No fixed treatment duration was specified. Patients in the study were planned to receive the treatment until disease progression (assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)), unacceptable toxicity, death, or discontinuation from study treatment for any other reason.

Conditions

• Neoplasms
• Breast Neoplasms
• Kidney Neoplasms
• Pancreatic Neuroendocine Neoplasms (pNETs)

Interventions

Type	Name	Description
DRUG	alpelisib	alpelisib is administered orally once a day on a continuous dosing schedule and dosed on a flat-fixed dose and not adjusted by body weight or body surface area, starting on Day 8 of Cycle 1 in the dose escalation and Day 1 of Cycle 1 in the dose expansion. In the doublet dose escalation, the alpelisib starting dose is 300 mg. The alpelisib dose may be escalated or de-escalated, as needed. In the triplet dose escalation part, the alpelisib starting dose is one dose level lower of the MTD as determined during the doublet escalation. The alpelisib dose may be escalated or de-escalated, as needed. In the doublet dose expansion and triplet dose expansion (patients assigned to alpelisib, everolimus and exemestane), alpelisib is administered at the recommended dose determined in the dose escalation. In the triplet dose expansion (patients assigned to alpelisib and exemestane), alpelisib is administered at a dose of 250 mg daily.
DRUG	everolimus	everolimus is administered orally once a day on a continuous dosing schedule and dosed on a flat-fixed dose and not adjusted by body weight or body surface area, starting on Day 1 of cycle 1 in both the dose escalation and dose expansion parts. In the dose escalation part, the everolimus starting dose is 2,5 mg. In the dose expansion part, everolimus is administered at the recommended dose determined in the dose escalation.
DRUG	exemestane	exemestane is administered orally once a day on a continuous dose of 25 mg starting on Day 1 of Cycle 1 in both the dose escalation and dose expansion.

Timeline

• Start date: 2014-05-14
• Primary completion: 2019-04-12
• Completion: 2019-04-12
• First posted: 2014-03-04
• Last updated: 2020-12-08

Locations

22 sites across 9 countries: United States, France, Germany, Hong Kong, Hungary, Italy, Netherlands, Spain, United Kingdom