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A Study of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as Initial Treatment for Participants With Triple-Negative Breast Cancer That Has Spread

NCT02322814

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Cobimetinib</span> in Combination With <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> as First-line Treatment for Patients With Metastatic Triple-negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: A Study of Cobimetinib in Combination With Paclitaxel as First-line Treatment for Patients With Metastatic Triple-negative Breast Cancer
  • Official Title:
  • Clinical Trial IDs

    NCT ID: NCT02322814

    ORG ID: WO29479

    NCI ID: 2014-002230-32

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    cobimetinib GDC-0973; RO5514041; XL518 cobimetinib + paclitaxel, safety run-in
    paclitaxel cobimetinib + paclitaxel, placebo + paclitaxel, safety run-in
    placebo placebo + paclitaxel

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    cobimetinib + paclitaxel Experimental Randomized double-blind expansion stage cobimetinib, paclitaxel
    placebo + paclitaxel Placebo Comparator Randomized double-blind expansion stage paclitaxel, placebo
    safety run-in Experimental Open-label cobimetinib, paclitaxel

    Eligibility 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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival, as determined by investigator using RECIST v1.1

    Incidence of adverse events (AEs), graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v4.0

    Secondary Outcome Measures

    Overall survival

    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

    Pharmacokinetic parameters of cobimetinib and paclitaxel (safety run-in stage): total exposure (AUC0-t), maximum and minimum concentrations (Cmax, Cmin) [composite outcome measure]

    Pharmacokinetic parameters of cobimetinib (expansion stage): total exposure (AUC0-t), maximum and minimum concentrations (Cmax, Cmin)

    Trial Keywords