Ignite Creation Date:
2025-12-24 @ 9:58 PM
Ignite Modification Date:
2026-01-05 @ 8:20 AM
Study NCT ID:
NCT03175432
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-11-03
First Post:
2017-05-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastases
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Phase II Study of BEvacizumab (Avastin) in Combination With Atezolizumab or Atezolizumab (Tencentriq) and Cobimetinib (Cotellic) in Patients With Untreated Melanoma Brain Metastases (TACo-BEAT-MBM)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well bevacizumab and atezolizumab with or without cobimetinib work in treating patients with untreated melanoma that has spread to the brain (brain metastases). Monoclonal antibodies, such as bevacizumab and atezolizumab, may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if giving bevacizumab and atezolizumab with or without cobimetinib will work better in treating patients with melanoma brain metastases.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the objective intracranial response rate of the combination of bevacizumab and atezolizumab in patients with active melanoma brain metastases (MBM) as measured by a modified immunotherapy Response Assessment in Neuro-oncology (iRANO) criteria measured by magnetic resonance imaging (MRI) of the brain.
II. To assess the safety, tolerability, and preliminary efficacy of the triplet combination of atezolizumab (Tencentriq), bevacizumab (Avastin), and cobimetinib (Cotellic). (TACo)
SECONDARY OBJECTIVES:
I. Safety and tolerability of bevacizumab + atezolizumab. II. Safety and tolerability of the combination of atezolizumab + bevacizumab + cobimetinib in patients with BRAFV600 wild-type metastatic melanoma to the brain who've experienced prior progression on anti-PD1.
III. Overall response rates (intracranial + extracranial) using a modified version of iRANO and compared to modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM).
IV. Duration of response intracranially and extracranially. V. Progression-free survival. VI. Overall survival. VII. Immune modulation. VIII. Changes in circulating cell free deoxyribonucleic acid (cfDNA) as determinants of response and markers of early progression.
IX. Changes in relative apparent diffusion coefficient as measured by MRI as early predictor of response.
X. Changes in neurocognitive function and health-related quality of life. XI. Molecular and immunological changes demonstrated in extracranial lesions.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles with atezolizumab and bevacizumab repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive cobimetinib orally (PO) thrice daily (TID) on days 1-21. Cycles with cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 3 months thereafter.
I. To determine the objective intracranial response rate of the combination of bevacizumab and atezolizumab in patients with active melanoma brain metastases (MBM) as measured by a modified immunotherapy Response Assessment in Neuro-oncology (iRANO) criteria measured by magnetic resonance imaging (MRI) of the brain.
II. To assess the safety, tolerability, and preliminary efficacy of the triplet combination of atezolizumab (Tencentriq), bevacizumab (Avastin), and cobimetinib (Cotellic). (TACo)
SECONDARY OBJECTIVES:
I. Safety and tolerability of bevacizumab + atezolizumab. II. Safety and tolerability of the combination of atezolizumab + bevacizumab + cobimetinib in patients with BRAFV600 wild-type metastatic melanoma to the brain who've experienced prior progression on anti-PD1.
III. Overall response rates (intracranial + extracranial) using a modified version of iRANO and compared to modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM).
IV. Duration of response intracranially and extracranially. V. Progression-free survival. VI. Overall survival. VII. Immune modulation. VIII. Changes in circulating cell free deoxyribonucleic acid (cfDNA) as determinants of response and markers of early progression.
IX. Changes in relative apparent diffusion coefficient as measured by MRI as early predictor of response.
X. Changes in neurocognitive function and health-related quality of life. XI. Molecular and immunological changes demonstrated in extracranial lesions.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles with atezolizumab and bevacizumab repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive cobimetinib orally (PO) thrice daily (TID) on days 1-21. Cycles with cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 3 months thereafter.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: