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A Study of Cobimetinib in Combination With Paclitaxel as First-line Treatment for Patients With Metastatic Triple-negative Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02322814
First received: December 19, 2014
Last updated: October 3, 2016
Last verified: October 2016
  Purpose
This multistage, randomized, Phase II, double-blind, multicenter, placebo-controlled trial will evaluate the safety and tolerability and estimate the efficacy of cobimetinib + paclitaxel versus placebo + paclitaxel in patients with metastatic or locally advanced, triple-negative adenocarcinoma of the breast that have not received prior systemic therapy for metastatic breast cancer (MBC). An open-label safety run-in stage of the combination cobimetinib + paclitaxel will undergo an Internal Safety Review before starting the enrollment of patients into the expansion double-blind stage of this study. Patients may continue on study treatment until the development of progressive disease, unacceptable toxicity, and/or consent withdrawal. The target sample size is 12 patients for the safety run-in stage and approximately 100 patients in the expansion stage.

Condition Intervention Phase
Breast Cancer
Drug: cobimetinib
Drug: paclitaxel
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival, as determined by investigator using RECIST v1.1 [ Time Frame: Until all patients enrolled have been followed until death, withdrawal of consent, lost to follow-up, or the Sponsor decides to end the study, whichever occurs first, approximately 3 years ]
  • Incidence of adverse events (AEs), graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v4.0 [ Time Frame: Up to 3 years ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 3 years ]
  • Objective response rate (partial response [PR] plus complete response [CR]), occurring after randomization and confirmed >/= 28 days later, as determined by the investigator using RECIST v1.1 [ Time Frame: Up to 3 years ]
  • Pharmacokinetic parameters of cobimetinib and paclitaxel (safety run-in stage): total exposure (AUC0-t), maximum and minimum concentrations (Cmax, Cmin) [composite outcome measure] [ Time Frame: Up to 28 days ]
  • Pharmacokinetic parameters of cobimetinib (expansion stage): total exposure (AUC0-t), maximum and minimum concentrations (Cmax, Cmin) [ Time Frame: Up to 3 years ]

Estimated Enrollment: 160
Study Start Date: March 2015
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cobimetinib + paclitaxel
Randomized double-blind expansion stage
Drug: cobimetinib
60 mg/day cobimetinib orally administered once a day (QD), on Day 3 through Day 23 of each 28-day treatment cycle
Other Name: GDC-0973; RO5514041; XL518
Drug: paclitaxel
Paclitaxel administered at a dose of 80 mg/m2 by IV infusion on Day 1, Day 8, and Day 15 of each 28-day cycle according to prescribing information
Placebo Comparator: placebo + paclitaxel
Randomized double-blind expansion stage
Drug: paclitaxel
Paclitaxel administered at a dose of 80 mg/m2 by IV infusion on Day 1, Day 8, and Day 15 of each 28-day cycle according to prescribing information
Drug: placebo
matching placebo to cobimetinib, orally administered once a day (QD), on Day 3 through Day 24 of each 28-day treatment cycle
Experimental: safety run-in
Open-label
Drug: cobimetinib
60 mg/day cobimetinib orally administered once a day (QD), on Day 3 through Day 23 of each 28-day treatment cycle
Other Name: GDC-0973; RO5514041; XL518
Drug: paclitaxel
Paclitaxel administered at a dose of 80 mg/m2 by IV infusion on Day 1, Day 8, and Day 15 of each 28-day cycle according to prescribing information

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of the breast with measurable metastatic or locally recurrent disease
  • Locally recurrent disease must not be amenable to resection with curative intent
  • Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1
  • Adequate hematologic and end organ function
  • Agreement to use highly effective contraceptive methods as stated in protocol

Exclusion Criteria:

  • Known HER2-, ER-, or PR-positive breast cancer by local laboratory assessment
  • Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)
  • Any systemic anticancer therapy within 3 weeks prior to Cycle 1, Day 1
  • Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
  • Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for major surgical procedure during the course of the study
  • Prior exposure to experimental treatment targeting Raf, MEK, or the MAPK pathway
  • Brain metastases (symptomatic or nonsymptomatic) that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days prior to first study treatment dose
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  • History of clinically significant cardiac dysfunction
  • Pregnancy (positive serum pregnancy test) or lactation
  • Uncontrolled serious medical or psychiatric illness
  • Active infection requiring intravenous (IV) antibiotics on Cycle 1, Day 1
  • Patients who have a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02322814

Contacts
Contact: Reference Study ID Number: WO29479 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 71 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02322814     History of Changes
Other Study ID Numbers: WO29479
2014-002230-32 ( EudraCT Number )
Study First Received: December 19, 2014
Last Updated: October 3, 2016

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Neoplasms
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 29, 2017