A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
NCT ID: NCT03273153
Last Updated: 2022-09-21
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
446 participants
INTERVENTIONAL
2017-12-11
2021-02-19
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cobimetinib and Atezolizumab
Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.
Cobimetinib
Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.
Atezolizumab
Atezolizumab 840 mg as IV infusion once in every 2 weeks.
Pembrolizumab
Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.
Pembrolizumab
Pembrolizumab 200 mg as IV infusion once in every 3 weeks.
Interventions
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Cobimetinib
Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.
Atezolizumab
Atezolizumab 840 mg as IV infusion once in every 2 weeks.
Pembrolizumab
Pembrolizumab 200 mg as IV infusion once in every 3 weeks.
Eligibility Criteria
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Inclusion Criteria
* Naive to prior systemic anti-cancer therapy for melanoma
* Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority
* A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study entry. If 20 slides are not available or the tissue block is not of sufficient size, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Age \>=18 years at time of signing Informed Consent Form
* Ability to comply with the study protocol, in the investigator's judgment
* Histologically or cytologically confirmed BRAFV600 wild-type melanoma
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy \>=3 months
* Adequate hematologic and end-organ function
* For women of childbearing potential: agreement to remain abstinent or use at least two forms of effective contraceptive with a failure rate of \< 1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib and at least 5 months after the last dose of atezolizumab or pembrolizumab
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (e.g. condom), and agreement to refrain from donating sperm, for at least 3 months after the last dose of cobimetinib
* Willingness and ability of patients to report selected study outcomes (e.g., GHS and HRQoL) using an electronic device or paper backup questionnaires.
Exclusion Criteria
* Malabsorption condition that would alter the absorption of orally administered medications
* Pregnancy, breastfeeding, or intention of becoming pregnant during the study
* History of severe hypersensitivity reactions to components of the cobimetinib, atezolizumab, or pembrolizumab formulations
* Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or systemic immunostimulatory/immunosuppresive medication
* Ocular melanoma
* Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation of needing such procedure while receiving study treatment
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
* Active or untreated central nervous system (CNS) metastases Exclusions Related to Cardiovascular Disease
* Unstable angina, new-onset angina within last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure classified as New York Heart Association Class II or higher
* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or \<50%, whichever is lower
* Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic baseline hypertension consistently above 159/99 mmHg despite optimal medical management
* History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
* HIV infection
* Active tuberculosis infection
* Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of Cycle 1
* Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
* Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular Disease
* Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and Immunomodulatory Drugs
* Active or history of autoimmune disease or immune deficiency
* Prior allogeneic stem cell or solid organ transplantation
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1, Cycle 1 Exclusions Related to Other Medical Conditions or Medications
* Active malignancy (other than melanoma) or a prior malignancy within the past 3 years
* Any Grade \>=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
* History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
* Proteinuria \>3.5 gm/24 hr
* Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study treatment
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_CHAIR
Hoffmann-La Roche
Locations
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University of Arizona Cancer Center
Tucson, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC Norris Cancer Center
Los Angeles, California, United States
USC Norris Cancer Center; USC Oncology Hematology Newport Beach
Newport Beach, California, United States
University of California at Irvine Medical Center; Department of Oncology
Orange, California, United States
Stanford Comprehensive Cancer Center
Stanford, California, United States
UF Health Cancer Center at Orlando Health
Orlando, Florida, United States
Florida Cancer Specialist, North Region
St. Petersburg, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Northwestern University
Chicago, Illinois, United States
Massachusetts General Hospital;Hematology/ Oncology
Boston, Massachusetts, United States
University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
Ann Arbor, Michigan, United States
Dartmouth-Hitchcock Medical Center; Hematology/Oncology
Lebanon, New Hampshire, United States
Morristown Medical Center
Morristown, New Jersey, United States
Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists
Winston-Salem, North Carolina, United States
TriHealth Hatton Institute; Surgical Education
Cincinnati, Ohio, United States
St. Luke's University Health network
Bethlehem, Pennsylvania, United States
Thomas Jefferson University Hospital;Medical Oncology
Philadelphia, Pennsylvania, United States
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
M.D Anderson Cancer Center; Uni of Texas At Houston
Houston, Texas, United States
West Virginia University Hospitals Inc
Morgantown, West Virginia, United States
Cairns Base Hospital
Cairns, Queensland, Australia
Townsville General Hospital
Douglas, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
Cliniques Universitaires St-Luc
Brussels, , Belgium
AZ Groeninge
Kortrijk, , Belgium
UZ Leuven Gasthuisberg
Leuven, , Belgium
Instituto Nacional de Cancer - INCa; Oncologia
Rio de Janeiro, Rio de Janeiro, Brazil
Hospital das Clinicas - UFRGS
Porto Alegre, Rio Grande do Sul, Brazil
Hopital Avicenne; Dermatologie
Bobigny, , France
Hopital Saint Andre CHU De Bordeaux; Dermatologie
Bordeaux, , France
Chu Site Du Bocage;Dermatologie
Dijon, , France
CHU de Grenoble - Hôpital Nord
Grenoble, , France
Centre Hospitalier Le Mans; Dermatologie
Le Mans, , France
Hopital Claude Huriez; Sce Dermatologie
Lille, , France
Hopital Timone Adultes; Dermatologie
Marseille, , France
CHU de Nantes; Cancéro-dermatologie
Nantes, , France
Hopital l Archet 2; Ginestriere, Service de; Dermatologie
Nice, , France
Groupe Hospitalier Bichat Claude Bernard
Paris, , France
Hopital Saint Louis; Dermatologie 1
Paris, , France
Hopital Robert Debre; DERMATOLOGIE
Reims, , France
Centre Eugene Marquis; Service d'oncologie
Rennes, , France
Hopital Charles Nicolle; Dermatologie Serv.
Rouen, , France
Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
Toulouse, , France
Institut Gustave Roussy; Dermatologie
Villejuif, , France
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie
Dresden, , Germany
HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie
Erfurt, , Germany
Universitatsklinikum Essen; Klinik für Dermatologie
Essen, , Germany
Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
Frankfurt, , Germany
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
Gera, , Germany
Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
Hanover, , Germany
UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
Kiel, , Germany
Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie
Mainz, , Germany
Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie
Mannheim, , Germany
Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin
Minden, , Germany
Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie
München, , Germany
Fachklinik Hornheide; Dermatologie
Münster, , Germany
Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
Tübingen, , Germany
Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine
Athens, , Greece
Laiko General Hospital Athen
Athens, , Greece
Metropolitan Hospital; Dept. of Oncology
Pireaus, , Greece
Bioclinic Thessaloniki
Thessaloniki, , Greece
Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
Budapest, , Hungary
Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika
Pécs, , Hungary
University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology
Szeged, , Hungary
A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana
Bari, Apulia, Italy
Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
Napoli, Campania, Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
Napoli, Campania, Italy
A.O. Universitaria Policlinico Di Modena; Ematologia
Modena, Emilia-Romagna, Italy
IFO - Istituto Regina Elena; Oncologia Medica
Rome, Lazio, Italy
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
Genoa, Liguria, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milan, Lombardy, Italy
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
Milan, Lombardy, Italy
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
Candiolo, Piedmont, Italy
Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico
Pisa, Tuscany, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, Veneto, Italy
Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde
Amsterdam, , Netherlands
Amphia Ziekenhuis, locatie Langendijk;Oncology
Breda, , Netherlands
Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
Rotterdam, , Netherlands
Zuyderland ziekenhuis locatie Geleen
Sittard-Geleen, , Netherlands
Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
Gdansk, , Poland
COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
Lublin, , Poland
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
Poznan, , Poland
Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
Szczecin, , Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, , Poland
Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii
Wroclaw, , Poland
Moscow City Oncology Hospital #62
Moscovskaya Oblast, Moscow Oblast, Russia
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
Moscow, , Russia
St. Petersburg Oncology Hospital
Saint Petersburg, , Russia
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
Saint Petersburg, , Russia
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital, Yonsei University Health System
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Hospital Universitario Son Espases; Servicio de Oncologia
Palma de Mallorca, Balearic Islands, Spain
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Badalona, Barcelona, Spain
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
Santiago de Compostela, LA Coruña, Spain
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
Las Palmas de Gran Canaria, LAS Palmas, Spain
Clinica Universitaria de Navarra; Servicio de oncología
Pamplona, Navarre, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, , Spain
Hospital Clínic i Provincial; Servicio de Oncología
Barcelona, , Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
Madrid, , Spain
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, , Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, , Spain
Hospital Universitario La Paz; Servicio de Oncologia
Madrid, , Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
Seville, , Spain
Instituto Valenciano Oncologia; Oncologia Medica
Valencia, , Spain
Hospital General Universitario de Valencia; Servicio de oncologia
Valencia, , Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
Zaragoza, , Spain
BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
Bristol, , United Kingdom
Western General Hospital; Edinburgh Cancer Center
Edinburgh, , United Kingdom
Leicester Royal Infirmary; Dept. of Medical Oncology
Leicester, , United Kingdom
University College London Hospital
London, , United Kingdom
Guys & St Thomas Hospital; Department of Oncology
London, , United Kingdom
University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
Stoke-on-Trent, , United Kingdom
Singleton Hospital; Pharmacy
Swansea, , United Kingdom
Royal Cornwall Hospital
Truro, , United Kingdom
Countries
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References
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de Azevedo SJ, de Melo AC, Roberts L, Caro I, Xue C, Wainstein A. First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2016-004387-18
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CO39722
Identifier Type: -
Identifier Source: org_study_id
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