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

Running, not enrolling · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT03175432

Run by

M.D. Anderson Cancer Center

People needed

29

Starts

2017-06-15

Expected to finish

2028-06-30

Last updated by the study team

2026-06-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN with the following exception: 1) patients with documented liver metastases: AST and/or ALT =< 5 x ULN
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Alkaline phosphatase =< 2.5 x ULN with the following exception: 1) =< 5 x ULN in patients with documented liver metastases =< 7 x ULN in patients with documented bone metastases
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Serum creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
• Obtained within 14 days prior to the first study treatment (cycle 1, day 1): Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein =< 1 g of protein is demonstrated
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for at least 12 months after the last dose of atezolizumab
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN within 7 days prior to study enrollment

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)
• Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan a) history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection; a) Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible; b) Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
• Active tuberculosis
• Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
• Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study a) Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to cycle 1, day 1 or at any time during the study
• Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score =< 6, and prostate-specific antigen [PSA] =< 10 mg/mL, etc.)
• Known hypersensitivity to any component of bevacizumab, atezolizumab, or cobimetinib

Where it is running

• M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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