Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastases

NCT03175432 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2016-0866NCI-2018-01188
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

BRAF V600 Wild Type; Clinical Stage IV Cutaneous Melanoma AJCC v8; Intracranial Melanoma; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Refractory Melanoma

Outcome Measures

Primary Outcomes (2)

• Objective intracranial response rate (OIRR) as measured by the modified immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria

  Each response rate measure will be summarized using frequencies and percentages overall and by cohort. In addition, 90% exact confidence intervals will be presented for each response rate measure, for all patients and by cohort.

  Up to 3 years

• Safety, tolerability, and efficacy of atezolizumab, bevacizumab, and cobimetinib (Arm II)

  Safety assessments will consist of monitoring and reporting adverse events (AEs) and serious adverse events (SAEs) that are considered related to atezolizumab. Bevacizumab and cobimetinib, all events of death, and any study-specific issue of concern summaries of AEs and SAEs with respect to incidence, severity, and causality will be provided for all patients and by cohort. In addition, discontinuation due to AEs, SAEs and deaths will be summarized. Patients will also be evaluated for dose-limiting toxicities through the first cycle.

  Up to 3 years

Secondary Outcomes (6)

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Arm I)

  Up to 3 years

• Incidence of adverse events graded according to CTCAE version 4.0 (Arm II)

  Up to 3 years

• Overall response rates (intracranial + extracranial) using 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)

  Up to 3 years

• Duration of response (DOR)

  From date of first response to date of disease progression, assessed up to 3 years

• Progression-free survival

  From treatment start date to date of disease progression or death, assessed up to 3 years

Study Arms (2)

Arm I (atezolizumab, bevacizumab)

EXPERIMENTAL

Participants receive atezolizumab 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.

Drug: Atezolizumab; Biological: Bevacizumab; Procedure: Quality-of-Life Assessment

Arm II (atezolizumab, bevacizumab, cobimetinib)

EXPERIMENTAL

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 PO TID on days 1-21. Cycles with cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Biological: Bevacizumab; Drug: Cobimetinib; Procedure: Quality-of-Life Assessment

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Arm I (atezolizumab, bevacizumab); Arm II (atezolizumab, bevacizumab, cobimetinib)

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

Arm I (atezolizumab, bevacizumab); Arm II (atezolizumab, bevacizumab, cobimetinib)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Arm II (atezolizumab, bevacizumab, cobimetinib)

Quality-of-Life Assessment PROCEDURE

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (atezolizumab, bevacizumab); Arm II (atezolizumab, bevacizumab, cobimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF)
• Age \>/= 18 years
• Ability and willingness to comply with the requirements of the study protocol
• Life expectancy \> 12 weeks
• Asymptomatic off steroids for at least 10 days except patients: a) who have mild symptoms from intracranial disease that do not affect their performance status; or b) who are asymptomatic, but require steroids for control of symptoms on a maximum dose of dexamethasone 4mg/day orally (PO) or equivalent
• Prior therapies for extracranial metastatic melanoma including chemotherapy, BRAFi/MEKi, cytokine or vaccine therapy as long as it did not include PD-1/PD-L1. Note: Patients who are PD-1 refractory are allowed to enroll into the TACo arm if BRAFV600 wild-type is confirmed. Patients that are known to have BRAFV600 mutation must have received prior BRAFi/MEKi prior to enrolling on TACo. Patients that have received prior BRAF/MEKi have to have received their last dose of BRAF/MEKi \> 3 months prior to being treated on this study.
• At least one measurable intracranial target lesion for which all of the following criteria are met: a) Previously untreated or progressive after previous local therapy b) Immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy c) Largest diameter of \>= 0.5 cm, but =\< 3 cm as determined by contrast-enhanced MRI
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 4 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression a) Tumor tissue should be of good quality based on total and viable tumor content. Fine needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable. For core-needle biopsy specimens, at least three cores should be submitted for evaluation. b) Patients who do not have tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. c) Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable
• Histologically or cytologically confirmed BRAFV600 wild-type melanoma through archival or newly obtained tissue.(only patients who are PD-1 refractory who will enroll onto the TACo arm)
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Absolute neutrophil count (ANC) \>= 1500 cells/u
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): White blood cell (WBC) counts \> 2500/uL
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Lymphocyte count \>= 500/uL
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Platelet count \>= 100,000/uL
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Hemoglobin \>= 9.0 g/dL
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Total bilirubin =\< 1.5 x upper limit of normal (ULN) with the following exception: 1) patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled

You may not qualify if:

• Symptomatic brain metastases requiring immediate local interventions such as craniotomy or stereotactic radiosurgery (SRS)
• Patients who require immediate surgical or radiotherapy interventions
• Increasing corticosteroid dose in 7 days prior to administration of first dose of study drug. Symptomatic patients who have stable or decreasing corticosteroid use in the past 7 days may be included
• Patients with leptomeningeal disease
• Any approved anticancer therapy, including chemotherapy and hormonal therapy within 3 weeks prior to initiation of study treatment; however, the following are allowed: a) Hormone-replacement therapy or oral contraceptives b) Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
• Current, recent (within 3 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Adverse events (AEs) from prior anticancer therapy that have not resolved to grade =\< 1 except for alopecia
• Bisphosphonate therapy for symptomatic hypercalcemia a) Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
• Patients who are pregnant, lactating, or breastfeeding
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Inability to undergo MRI secondary to: a) metal b) claustrophobia c) gadolinium contrast allergy
• Prior radiation therapy within the last 14 days
• Inability to comply with study and follow-up procedures
• History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis a) Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. b) Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. c) Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations; rash must cover less than 10% of body surface area (BSA)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

atezolizumab; Bevacizumab; Immunoglobulin G; Disulfides; cobimetinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Hussein A Tawbi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 5, 2017
• Study Start: June 15, 2017
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 25, 2026

Record last verified: 2026-06

Locations

US (1)