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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02788279




Registration number
NCT02788279
Ethics application status
Date submitted
27/05/2016
Date registered
2/06/2016
Date last updated
11/12/2019

Titles & IDs
Public title
A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)
Scientific 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
Secondary ID [1] 0 0
2016-000202-11
Secondary ID [2] 0 0
GO30182
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody
Treatment: Drugs - Cobimetinib
Treatment: Drugs - Regorafenib

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.

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization up to death due to any cause (up to approximately 20 months)
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Timepoint [1] 0 0
From randomization up to disease progression or death due to any cause (up to approximately 20 months)
Secondary outcome [2] 0 0
Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1
Timepoint [2] 0 0
From randomization up to death due to any cause (up to approximately 20 months)
Secondary outcome [3] 0 0
Duration of Response (DOR) According to RECIST Version 1.1
Timepoint [3] 0 0
From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline, end of the study (up to approximately 2.5 years)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline, end of the study (up to approximately 2.5 years)
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [6] 0 0
Baseline, end of the study (up to approximately 2.5 years)
Secondary outcome [7] 0 0
Plasma Concentration of Cobimetinib
Timepoint [7] 0 0
Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) (up to approximately 2.5 years).
Secondary outcome [8] 0 0
Serum Concentration of Atezolizumab
Timepoint [8] 0 0
Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 2.5 years. Detailed time frame is explained in the outcome measure description field.
Secondary outcome [9] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Timepoint [9] 0 0
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 2.5 years) (1 cycle = 28 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/12/2018
Sample size
Target
Accrual to date
Final
363
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Port Macquarie Base Hospital;North Coast Cancer Institute - Port Macquarie
Recruitment hospital [2] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [3] 0 0
Sydney Adventist Hospital; Clinical Trial Unit - Sydney
Recruitment hospital [4] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment hospital [5] 0 0
Peninsula and South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [6] 0 0
Austin Health; Cancer Clinical Trial Centre - Heidelberg
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2076 - Sydney
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Belgium
State/province [14] 0 0
Bonheiden
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Charleroi
Country [17] 0 0
Belgium
State/province [17] 0 0
Kortrijk
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
British Columbia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Hong Kong
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Shatin
Country [25] 0 0
Italy
State/province [25] 0 0
Campania
Country [26] 0 0
Italy
State/province [26] 0 0
Emilia-Romagna
Country [27] 0 0
Italy
State/province [27] 0 0
Liguria
Country [28] 0 0
Italy
State/province [28] 0 0
Lombardia
Country [29] 0 0
Italy
State/province [29] 0 0
Puglia
Country [30] 0 0
Italy
State/province [30] 0 0
Toscana
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Gyeonggi-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Jeollanam-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Poland
State/province [34] 0 0
Bydgoszcz
Country [35] 0 0
Poland
State/province [35] 0 0
Gdansk
Country [36] 0 0
Poland
State/province [36] 0 0
Gdynia
Country [37] 0 0
Poland
State/province [37] 0 0
Krakow
Country [38] 0 0
Poland
State/province [38] 0 0
Lodz
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Arkhangelsk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Moscow
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Omsk
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Navarra
Country [45] 0 0
Spain
State/province [45] 0 0
Valencia
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Birmingham
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Manchester
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Oxford
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Romford
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Sheffield
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02788279
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02788279