Clinical trial NCT02322814
Conditions: Breast Cancer
Sponsor: Hoffmann-La Roche
Start date: 2015-03-12; Completion date: 2021-09-17
Enrollment: 169 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This three-cohort, multi-stage, randomized, Phase II, multicenter trial will evaluate the safety and tolerability and estimate the efficacy of cobimetinib plus paclitaxel versus placebo plus paclitaxel in Cohort I, of cobimetinib plus atezolizumab plus paclitaxel in Cohort II, and of cobimetinib plus atezolizumab plus nab-paclitaxel in Cohort III in participants with metastatic or locally advanced, triple-negative adenocarcinoma of the breast who have not received prior systemic therapy for metastatic breast cancer (MBC). Participants may continue on study treatment until the development of progressive disease (PD) or the loss of clinical benefit, unacceptable toxicity, and/or consent withdrawal. The Cohort I target sample size is 12 participants for the safety run-in stage and approximately 90 participants in the expansion stage. Each of Cohorts II and III will consist of a safety run-in stage of approximately 15 participants followed by an expansion stage of approximately 15 participants.

Detailed description:

Arms: arm 1: Participants will receive a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study. arm 2: Participants will receive a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study. arm 3: Participants will receive cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study. arm 4: Participants will receive cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
Interventions: intervention 1: Cobimetinib intervention 2: Paclitaxel intervention 3: Placebo intervention 4: Atezolizumab intervention 5: Nab-Paclitaxel
Intervention descriptions: intervention 1: Cobimetinib will be administered orally at a dose of 60 milligrams (mg) per day, once a day, on Day 3 through Day 23 of each 28-day treatment cycle. intervention 2: Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion on Day 1, Day 8, and Day 15 of each 28-day cycle according to prescribing information. intervention 3: Placebo matching to cobimetinib will be administered orally, once a day, on Day 3 through Day 23 of each 28 day treatment cycle. intervention 4: Atezolizumab will be administered to Cohorts II and III at a dose of 840 mg IV every 2 weeks on Days 1 and 15 of each 28-day treatment cycle. intervention 5: Nab-Paclitaxel will be administered to Cohort III according to the local prescribing information at a starting dose of 100 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Protocol documents:
Prot_SAP_000.pdf: 
Official Title: 
A Multistage, Phase II Study Evaluating the Safety and Efficacy 
of Cobimetinlb plus Paclitaxel, Coblmetlnib plus Atezolizumab 
plus Paclitaxel, or Cobimetinib plus Atezolizumab plus Nab­
Paclitaxel as First-Line Treatment for Patients with Metastatic 
Triple-Negative Breast Cancer 
NCT Number: 
NCT02322814 
Document Date: Protocol Version 8:  25-Oct-2018