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A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02788279
First received: May 27, 2016
Last updated: June 26, 2017
Last verified: June 2017
  Purpose
This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.

Condition Intervention Phase
Colorectal Cancer Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody Drug: Cobimetinib Drug: Regorafenib Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III, Open-Label, Multicenter, Three-Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy vs. Regorafenib in Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline up to death due to any cause (up to approximately 3 years) ]

Secondary Outcome Measures:
  • Progression-Free Survival (PFS) According to RECIST Version 1.1 [ Time Frame: From randomization up to disease progression or death due to any cause (up to approximately 3 years) ]
  • Percentage of Participants with Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1 [ Time Frame: From randomization up to disease progression or death due to any cause (up to approximately 3 years) ]
  • Duration of Response (DOR) According to RECIST Version 1.1 [ Time Frame: From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 3 years) ]
  • Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score at the End of the Study [ Time Frame: Baseline, end of the study (up to approximately 3 years) ]
  • Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study [ Time Frame: Baseline, end of the study (up to approximately 3 years) ]
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to end of the study (up to approximately 3 years) ]
  • Plasma Concentration of Cobimetinib [ Time Frame: Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 3 years. Detailed time frame is explained in the outcome measure description field. ]
    Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infusion on Day 1 of Cycles 1 and 4; pre-infusion (0 hours) on Day 1 of Cycle 8 and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 3 years) (1 cycle = 28 days)

  • Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4, 8, and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 3 years) (1 cycle = 28 days) ]
  • EuroQoL 5 Dimensions (EQ-5D-5L) Questionnaire Score [ Time Frame: At the end of the study (up to approximately 3 years) ]

Estimated Enrollment: 360
Actual Study Start Date: July 5, 2016
Estimated Study Completion Date: February 7, 2019
Estimated Primary Completion Date: February 7, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atezolizumab
Participants will receive atezolizumab monotherapy 1200 milligrams (mg) intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Experimental: Cobimetinib + Atezolizumab
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Active Comparator: Regorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Regorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

  Eligibility

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

Inclusion Criteria:

Disease-specific inclusion criteria:

  • Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer [AJCC] 7th edition)
  • Experienced disease progression or was intolerant to at least two systemic chemotherapy regimens for metastatic colorectal cancer that must have included fluroropyrimidines, irinotecan, and oxaliplatin; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion; disease progression must have occurred within 3 months of the last systemic therapy administration

General inclusion criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Anticipated life expectancy greater than or equal to (>=) 3 months
  • Adequate hematologic and end organ function
  • Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of less than [<] 1 percent [%] per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib
  • Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier contraception during the treatment period and for 3 months after the last dose of either cobimetinib or regorafenib
  • Provide an archival or newly obtained tumor tissue sample

Exclusion Criteria:

  • After the approximate 5% cap for microsatellite (MSI)-high participants is reached, only MSI-stable participants will be eligible
  • Once the 50% cap for wild-type RAS has been reached, only extended RAS-mutant participants will be eligible
  • Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment
  • Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1
  • Uncontrolled tumor-related pain. Participants requiring narcotic pain medication must be on a stable regimen at study entry
  • Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
  • Active or untreated central nervous system (CNS) metastases are excluded
  • Prior therapy with any cancer immunotherapy, MEK inhibitor, or regorafenib
  • Participants with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
  • Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%, whichever is lower
  • Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 millimeters of Mercury (mmHg) despite optimal medical management
  • Human immunodeficiency virus (HIV) infection
  • Active tuberculosis infection
  • Severe infections within 2 weeks prior to Cycle 1 Day 1
  • Active or chronic viral hepatitis B or C infection
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
  • Participants will be excluded if they currently have any of the risk factors as defined in the study protocol for retinal vein occlusion
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
  • History of organ transplantation including allogeneic bone marrow transplantation
  • Inability to swallow medications
  • Malabsorption condition that would alter the absorption of orally administered medications
  • Pregnant, lactating, breastfeeding, or intending to become pregnant during the study
  • Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study
  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: NCT02788279

  Show 90 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: NCT02788279     History of Changes
Other Study ID Numbers: GO30182
2016-000202-11 ( EudraCT Number )
Study First Received: May 27, 2016
Last Updated: June 26, 2017

Keywords provided by Hoffmann-La Roche:
Locally advanced or Metastatic colorectal adenocarcinoma

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 29, 2017