Breast Cancer Clinical Trial

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

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.

View Eligibility Criteria

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 advanced disease
Locally advanced disease must not be amenable to resection with curative intent
Measurable disease, according to RECIST, v1.1
Adequate hematologic and end organ function
Agreement to use highly effective contraceptive methods as stated in protocol

Exclusion Criteria:

Disease-Specific Exclusion Criteria

Known HER2-, ER-positive, 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 rapidly accelerated fibrosarcoma (Raf), MAP kinase/ERK kinase (MEK), or the mitogen-activated protein kinase (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 30 days prior to first study treatment dose

Cobimetinib-Specific Exclusion Criteria

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
Cobimetinib is metabolized by the hepatic cytochrome P3A4 (CYP3A4) enzyme. Drugs CYP3A4/5 inhibitors and inducers should be avoided

Atezolizumab-Specific Exclusion Criteria (Cohorts II and III Only)

History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
History of autoimmune disease
Prior allogenic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis (including pneumonitis), drug induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Positive test for Human Immunodeficiency Virus (HIV)
Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] or positive hepatitis B virus [HBV] deoxyribonucleic acid [DNA] test at screening) or hepatitis C
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibodies
Treatment with systemic immunostimulatory agents (including but not limited to interferons or Interlukin-2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial

Cardiac Exclusion Criteria

History of clinically significant cardiac dysfunction
Corrected QT interval at screening greater than (>) 480 milliseconds (ms) (average of triplicate screening measurements)
Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50 percent (%), whichever is lower

General Exclusion Criteria

No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assay
Pregnancy (positive serum pregnancy test) or lactation
Uncontrolled serious medical or psychiatric illness
Active infection requiring IV antibiotics on Cycle 1, Day 1
Participants who have a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil) or to nab-paclitaxel and any of the excipients

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

169

Study ID:

NCT02322814

Recruitment Status:

Completed

Sponsor:

Hoffmann-La Roche

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There are 51 Locations for this study

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Mercy Hospital, a Campus of Plantation General Hospital
Miami Florida, 33133, United States
Cancer Specialists of North Florida
Orange Park Florida, 32073, United States
Florida Hospital Cancer Inst
Orlando Florida, 32804, United States
Florida Cancer Research Institute
Plantation Florida, 33324, United States
Cancer Treatment Centers of America
Newnan Georgia, 30265, United States
Ingalls Memorial Hospital
Harvey Illinois, 60426, United States
Montefiore Einstein Cancer Center
Bronx New York, 10461, United States
Magee Womens Hospital
Pittsburgh Pennsylvania, 15213, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Avera Cancer Institute
Sioux Falls South Dakota, 57105, United States
Northwest Medical Specialties
Tacoma Washington, 98405, United States
Calvary Mater Newcastle
Waratah New South Wales, 2298, Australia
Mater Adult Hospital
South Brisbane Queensland, 4101, Australia
Peter MacCallum Cancer Centre; Medical Oncology
Melbourne Victoria, 3000, Australia
St John of God Murdoch Hospital; Oncology West
Murdoch Western Australia, 6150, Australia
Clinique Edith Cavell
Bruxelles , 1180, Belgium
AZ Sint Lucas (Sint Lucas)
Gent , 9000, Belgium
Jessa Zkh (Campus Virga Jesse)
Hasselt , 3500, Belgium
AZ Groeninge
Kortrijk , 8500, Belgium
AZ Sint Augustinus Veurne
Veurne , 8630, Belgium
Fakultni nemocnice Hradec Kralove
Hradec Kralove , 500 0, Czechia
Multiscan s.r.o.
Pardubice , 532 0, Czechia
Centre Oscar Lambret
Lille , 59020, France
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
Montpellier , 34298, France
Hopital Tenon
Paris , 75020, France
Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer
Rennes , 35000, France
Chaim Sheba Medical Center
Ramat Gan , 52656, Israel
Azienda Ospedaliero Universitaria Seconda Università Degli Studi Di Napoli
Napoli Campania, 80131, Italy
A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2
Bologna Emilia-Romagna, 40138, Italy
Centro Di Riferimento Oncologico; SOC Oncologia Medica C
Aviano Friuli-Venezia Giulia, 33081, Italy
Policlinico Universitario Agostino Gemelli
Roma Lazio, 00168, Italy
Istituto Europeo Di Oncologia
Milano Lombardia, 20141, Italy
Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico
Pisa Toscana, 56126, Italy
National Cancer Center; Medical Oncology
Gyeonggi-do , 410-7, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Korea University Guro Hospital
Seoul , 08308, Korea, Republic of
Yonsei University Health System/Severance Hospital
Seoul , 120-7, Korea, Republic of
Riga East Clinical University Hospital Latvian Oncology Centre
Riga , LV-10, Latvia
Pauls Stradins Clinical University Hospital
RÄ«ga , LV-10, Latvia
Prof. Dr. I. Chiricuta Institute of Oncology
Cluj Napoca , 40001, Romania
Oncology Center Sf. Nectarie
Craiova , 20034, Romania
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
Sabadell Barcelona, 8208, Spain
Organización Sanitaria Integrada Bilbao Basurto
Bilbao Vizcaya, 48013, Spain
Hospital Universitario Infanta Cristina; Servicio de Oncologia
Badajoz , 06080, Spain
Hospital Universitario Ramon y Cajal
Madrid , 28034, Spain
Fundacion Jimenez Diaz; Servicio de Oncologia
Madrid , 28040, Spain
Hospital Clinico San Carlos; Servicio de Nefrologia
Madrid , 28040, Spain
Hosp. Regional Univ. de Malaga - Hospital Materno Infantil; Hospital Materno Infantil de Malaga
Malaga , 29011, Spain
Chang Gung Memorial Hospital
Kaohsiung Country , 833, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
Taipei City , 11259, Taiwan
Nuffield Health Bournemouth Hospital
Bournemouth , BH1 1, United Kingdom
Mount Vernon Hospital
Middlesex , HA6 2, United Kingdom
Nottingham University Hospitals City Campus
Nottingham , NG5 1, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

169

Study ID:

NCT02322814

Recruitment Status:

Completed

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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