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

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

  • Cancer
  • Breast Cancer
  • Triple Negative Breast Cancer
Please note that the recruitment status of the study at your site may differ from the overall study status because some study sites may recruit earlier than others.
Study Status:

Terminated

This study runs in
Cities
  • Badajoz
  • Bilbao
  • Bologna
  • Bournemouth
  • c-r-o--ospedale
  • Charleston
  • Cluj-Napoca
  • Craiova
  • Gent
  • Goyang-si
  • Harvey
  • Hasselt
  • Jacksonville
  • Kaohsiung City
  • Kortrijk
  • Královéhradecký kraj
  • Lille
  • Lombardia
  • Madrid
  • Melbourne
  • Miami
  • Montpellier
  • Murdoch
  • Málaga
  • Napoli
  • New York
  • Northwood
  • Nottingham
  • Orlando
  • Pardubický kraj
  • Paris
  • Pisa
  • Pittsburgh
  • Plantation
  • Ramat Gan
  • Rennes
  • Roma
  • Rīga
  • Sabadell
  • Seoul
  • Sioux Falls
  • South Brisbane
  • Tacoma
  • Taipei City
  • Veurne
  • Waratah
Trial Identifier:

NCT02322814 2014-002230-32 WO29479

  • A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2

    9 Via Giuseppe Massarenti40138BolognaItaly
  • Asan Medical Center

    05505SeoulSouth Korea
  • Avera Cancer Institute

    1000 E 23rd St57105Sioux FallsUnited States
  • AZ Groeninge

    8500KortrijkBelgium
  • AZ Sint Augustinus Veurne

    100 Ieperse Steenweg8630VeurneBelgium
  • AZ Sint Lucas (Sint Lucas)

    1 Groenebriel9000GentBelgium
  • Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

    67 Via Roma56126PisaItaly
  • Azienda Ospedaliero Universitaria Seconda Università Degli Studi Di Napoli

    80131NapoliItaly
  • Calvary Mater Newcastle

    2298WaratahAustralia
  • Cancer Specialists of North Florida

    32256-6932JacksonvilleUnited States
  • Cancer Treatment Centers of America

    931 Lower Fayetteville Rd30263
  • Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

    35000RennesFrance
  • Centre Oscar Lambret

    59020LilleFrance
  • Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque

    208 Av. des Apothicaires34090MontpellierFrance
  • Centro Di Riferimento Oncologico; SOC Oncologia Medica C

    2 Via Franco Gallini33081c-r-o--ospedaleItaly
  • Chaim Sheba Medical Center

    2 Derech Sheba5265601Ramat GanIsrael
  • Chang Gung Memorial Hospital

    833Kaohsiung CityTaiwan
  • Clinique Edith Cavell

    1180
  • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

    1 Parc Taulí08208SabadellSpain
  • Fakultni nemocnice Hradec Kralove

    581 Sokolská500 05Královéhradecký krajCzechia
  • Florida Cancer Research Institute

    33324PlantationUnited States
  • Florida Hospital Cancer Inst

    2501 N Orange Ave32804OrlandoUnited States
  • Fundacion Jimenez Diaz; Servicio de Oncologia

    2 Av. de los Reyes Católicos28040MadridSpain
  • Hopital Tenon

    4 Rue de la Chine75020ParisFrance
  • Hosp. Regional Univ. de Malaga ? Hospital Materno Infantil; Hospital Materno Infantil de Malaga

    s/n Av. del Arroyo de los Ángeles29011MálagaSpain
  • Hospital Clinico San Carlos; Servicio de Nefrologia

    S/N Calle del Prof Martín Lagos28040MadridSpain
  • Hospital Universitario Infanta Cristina; Servicio de Oncologia

    06080BadajozSpain
  • Hospital Universitario Ramon y Cajal

    Km. 9 M-60728034MadridSpain
  • Ingalls Memorial Hospital

    1 Ingalls Dr60426HarveyUnited States
  • Istituto Europeo Di Oncologia

    435 Via Giuseppe Ripamonti20141LombardiaItaly
  • Jessa Zkh (Campus Virga Jesse)

    11 Stadsomvaart3500HasseltBelgium
  • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

    125號 Lide Rd112Taipei CityTaiwan
  • Korea University Guro Hospital

    08308SeoulSouth Korea
  • Magee Womens Hospital

    300 Halket St15213PittsburghUnited States
  • Mater Adult Hospital

    4101South BrisbaneAustralia
  • Medical University of South Carolina

    268 Calhoun St29425CharlestonUnited States
  • Mercy Hospital, a Campus of Plantation General Hospital

    3663 S Miami Ave33133MiamiUnited States
  • Montefiore Einstein Cancer Center

    1575 Blondell Ave10461New YorkUnited States
  • Mount Vernon Hospital

    HA6 2RNNorthwoodUnited Kingdom
  • Multiscan s.r.o.

    44 Kyjevská532 03Pardubický krajCzechia
  • National Cancer Center; Medical Oncology

    10408Goyang-siSouth Korea
  • Northwest Medical Specialties

    1624 S I St98405TacomaUnited States
  • Nottingham University Hospitals City Campus

    NG5 1PBNottinghamUnited Kingdom
  • Nuffield Health Bournemouth Hospital

    67 Lansdowne RdBH1 1RWBournemouthUnited Kingdom
  • Oncology Center Sf. Nectarie

    200347CraiovaRomania
  • Organización Sanitaria Integrada Bilbao Basurto

    48013BilbaoSpain
  • Pauls Stradins Clinical University Hospital

    13 Pilsoņu iela1002RīgaLatvia
  • Peter MacCallum Cancer Centre; Medical Oncology

    305 Grattan St3052MelbourneAustralia
  • Policlinico Universitario Agostino Gemelli

    8 Largo Agostino Gemelli00136RomaItaly
  • Prof. Dr. I. Chiricuta Institute of Oncology

    34-36 Str. Republicii400015Cluj-NapocaRomania
  • Riga East Clinical University Hospital Latvian Oncology Centre

    4 Hipokrāta iela1038RīgaLatvia
  • St John of God Murdoch Hospital; Oncology West

    100 Murdoch Dr6150MurdochAustralia
  • Yonsei University Health System/Severance Hospital

    03722SeoulSouth Korea
    Show study locations

    The source of the below information is public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc.. It has been summarised and edited into simpler language. For more information about this clinical study see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov and/or https://euclinicaltrials.eu and/or https://www.isrctn.com.

    The below information is taken directly from public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc., and has not been edited.

    Results Disclaimer

    Study 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.

    Hoffmann-La Roche Sponsor
    Phase 2 Phase
    NCT02322814, WO29479, 2014-002230-32 Trial Identifier
    Cobimetinib, Paclitaxel, Placebo, Atezolizumab, Nab-Paclitaxel Treatments
    Breast Cancer Condition
    Official Title

    A Multistage, Phase II Study Evaluating the Safety and Efficacy of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as First-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer

    Eligibility Criteria

    All Gender
    ≥ 18 Years Age
    No Healthy Volunteers
    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

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