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Colorectal CancerPhase 1NCT02876224

Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors

A Phase 1 study testing Atezolizumab, Bevacizumab and Cobimetinib in people with Colorectal Cancer, run by Hoffmann-La Roche at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, multicenter, single-arm, two-stage, Phase Ib study designed to assess the safety, tolerability, and pharmacokinetics of oral cobimetinib with intravenous (IV) atezolizumab and bevacizumab in participants with metastatic colorectal cancer (mCRC) who have received and progressed on at least one… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Atezolizumab, Bevacizumab and Cobimetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
6 sitesin 2 countries
Study dates
30 Sep 2016to 25 Jun 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Histologically confirmed unresectable metastatic colorectal adenocarcinoma
  • Life expectancy at least 12 weeks
  • Progression on a prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan for unresectable metastatic colorectal adenocarcinoma
  • Measurable disease per RECIST v1.1
  • Adequate hematologic and end organ function
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  • Creatinine clearance greater than or equal to (>=) 30 milliliters per minute (mL/min)
  • For biopsy cohort, participants must be bevacizumab naive or received the last bevacizumab treatment at least 12 months prior to Cycle 1 Day 1 and according to the investigator's judgment the planned biopsies would not expose participants to substantially increased risk of complications
  • For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 180 days after the last study treatment
  • For men, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Who cannot join

  • More than one prior line of systemic therapy for advanced CRC
  • Participants with known microsatellite (MSI)-high status
  • Major surgery or significant traumatic injury within 60 days prior to enrollment
  • Minor surgical procedure within 15 days of study Cycle 1 Day 1
  • Untreated central nervous system (CNS) metastases
  • Treatment with any investigational agent or approved therapy within 28 days
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  • Malignancies other than colorectal cancer within 5 years prior to Cycle 1 Day 1
  • Prior radiation therapy within 30 days prior to study Cycle 1 Day 1 and/or persistence of radiation-related adverse effects
  • Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past
  • Spinal cord compression not definitively treated with surgery and/or radiation
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Current or recent use of therapeutic oral or parenteral anticoagulants or thrombolytic agents
  • Intake of St. John's wort or hyperforin (potent cytochrome P450 [CYP] 3A4 enzyme inducer) or grapefruit juice (potent CYP3A4 enzyme inhibitor) within 7 days prior to initiation of study treatment
  • 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 components of cobimetinib, atezolizumab, or bevacizumab formulations
  • Prior treatment with clusters of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockage therapies, anti-programmed death protein-1, anti-program death-ligand 1, mitogen-activated protein kinase (MEK) inhibitor
  • Proteinuria value > 1.0 g at screening
  • Uncontrolled glaucoma with intraocular pressure ≥ 21 mmHg
  • Hyperglycemia (fasting) ≥ Grade 2
  • Human Immunodeficiency Virus (HIV) infection
  • Active hepatitis B or hepatitis C
  • History of autoimmune disease, clinically significant cardiac or pulmonary dysfunction
  • Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 or at any time during the study and for at least 5 months after the last dose of study drug
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
  • Uncontrolled tumor pain

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • University Of Colorado

    Aurora, Colorado, 80045

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Sarah Cannon Research Inst.

    Nashville, Tennessee, 37203

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

Spain2 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

    Madrid, 28050

Other trials in Spain

About this study

Official title: A Phase Ib Open-Label Study Evaluating the Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Bevacizumab and Immunotherapy When Administered in Patients With Gastrointestinal and Other Tumors

This is an open-label, multicenter, single-arm, two-stage, Phase Ib study designed to assess the safety, tolerability, and pharmacokinetics of oral cobimetinib with intravenous (IV) atezolizumab and bevacizumab in participants with metastatic colorectal cancer (mCRC) who have received and progressed on at least one prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan. There are two stages in this study: Stage 1 (safety run-in phase) and Stage 2 (dose expansion phase with two cohorts, an expansion cohort and a biopsy cohort).

Being tested
Atezolizumab, Bevacizumab, Cobimetinib
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called RO5541267

    Atezolizumab 840 mg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.

  • BevacizumabDrug

    Also called RO4876646

    Bevacizumab 5 mg/kg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.

  • CobimetinibDrug

    Also called RO5514041

    Cobimetinib 60 mg or at dose determined during safety run-in phase will be administered orally once daily for 21 days of each 28-day cycle as specified in the arm descriptions.

Study groups in NCT02876224
Study groupRoleWhat they receive
Cobimetinib + Bevacizumab + Atezolizumab (Stage 1: SRP)ExperimentalStage 1 Safety Run-in Phase (SRP): Approximately 12 participants will receive cobimetinib 60 milligrams (mg) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 milligrams per kilogram (mg/kg) administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Upon determination of the safety and tolerability of the treatment regimen, the study will proceed to Stage 2: dose expansion phase. If the results from the safety run-in phase require dose reduction in cobimetinib, then an additional Stage 1 cohort will be opened. Treatment will continue until the participant has disease progression according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cobimetinib
Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: BC)ExperimentalStage 2 Biopsy Cohort (BC): Approximately 7 evaluable participants in the biopsy cohort in expansion phase will receive bevacizumab 5 mg/kg IV on Cycle 1 Days 1 and 15 (tumor biopsy on Cycle 1 Day 8) and cobimetinib (at dose determined during safety run-in phase) orally on Cycle 1 Day 15 to Cycle 2 Day 14 (tumor biopsy on Cycle 1 Day 22). From Cycle 2 onwards, participants will follow the same treatment regimen for bevacizumab and atezolizumab (optional tumor biopsy on Cycle 2 Day 22) as those in the safety run-in phase and expansion cohort, and for cobimetinib cycles start at Day 15 and will continue 21 days to Day 7 of next cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Biopsies must be collected before the initiation of cobimetinib and atezolizumab. Treatment will continue until disease progression according to RECIST v1.1, unacceptable toxicity, death, decision to withdraw, or pregnancy, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cobimetinib
Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: EC)ExperimentalStage 2 Expansion Cohort (EC): Approximately 14 participants will receive cobimetinib (at dose determined during safety run-in phase) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 mg/kg administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Treatment will continue until the participant has disease progression according to RECIST v1.1, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cobimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events

    Measured: Baseline up to approximately 12 months

Secondary outcomes (6)

  1. Plasma Maximum Concentration (Cmax) of Cobimetinib

    Measured: Safety run-in phase and expansion cohort: Predose (0 hours) on Cycle 1 Day 15 and Cycle 3 Day 15; 2 to 4 hours postdose on Cycle 1 Day 1 and Cycle 3 Day 15. Biopsy cohort: 0-2 hours predose and 2-4 hours postdose on Cycle 2 Day 1. Each cycle is 28 days.

  2. Plasma Minimum Concentration (Cmin) of Cobimetinib

    Measured: Safety run-in phase and expansion cohort: Predose (0 hours) on Cycle 1 Day 15 and Cycle 3 Day 15; 2 to 4 hours postdose on Cycle 1 Day 1 and Cycle 3 Day 15. Biopsy cohort: 0-2 hours predose and 2-4 hours postdose on Cycle 2 Day 1. Each cycle is 28 days.

  3. Serum Cmax of Atezolizumab

    Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycles 1, 2, 4, 8, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 1 Day 1 and Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.

    Measured: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)

  4. Serum Cmin of Atezolizumab

    Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycles 1, 2, 4, 8, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 1 Day 1 and Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.

    Measured: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)

  5. Serum Cmin of Bevacizumab

    Measured: Safety run-in phase and expansion cohort: prior to the infusion (0 hours) on Cycle 3 Day 15. Biopsy cohort: prior to the infusion (0 hours) on Cycle 3 Day 1. Each cycle is 28 days.

  6. Percentage of Participants with Anti-therapeutic Antibodies (ATAs) Response to Atezolizumab

    Safety run-in phase and expansion cohort: Prior to the infusion (0 hours) on Day 1 of Cycle 1, 2, 4, 8, and every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 3; 30 minutes after end of infusion (infusion duration 30-60 minutes) on Cycle 3 Day 15; at treatment discontinuation visit (up to 12 months). Biopsy cohort: prior to the infusion (0 hours) on Day 1 of Cycles 3, 5, 9, every 8 cycles thereafter (maximum up to 12 months) and on Day 15 of Cycle 4; 30 minutes after end of infusion on Day 15 of Cycle 4; at treatment discontinuation visit (up to 12 months). Each cycle is 28 days.

    Measured: Baseline up to approximately 12 months (detailed sample collection timepoints are provided in outcome measure description field)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2016 (estimated)
  2. Study start30 Sep 2016
  3. Primary completion25 Jun 2019
  4. Study completion25 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02876224
Sponsor's protocol ID
CO39083
Other IDs
2016-000584-16, 2016
Status last verified
Aug 2019
First submitted
18 Aug 2016
Last updated
13 Aug 2019
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Bevacizumab and Cobimetinib in people with Colorectal Cancer, run by Hoffmann-La Roche at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (time frame: Baseline up to approximately 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02876224.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.

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