A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases
Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
Hoffmann-La Roche
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
Histologically confirmed melanoma with radiologically confirmed brain metastases
Documented BRAFV600 mutation status of melanoma tumour tissue using a validated genetic test.
Measurable brain metastases
Age ≥18 years
Able to comply with the study protocol, in the investigator's judgment
ECOG Performance Status ≤ 2
Life expectancy of \> 3 months
Willing and able to complete health and quality of life questionnaires required by the protocol
Adequate hematologic and end-organ function
Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least six months after completion of study therapy.
Male patients must agree to refrain from donating sperm for at least six months after the last dose of cobimetinib
You may not be if
Prior SRT or surgical therapy of ≤ 10 brain metastases is allowed but prior WBRT is not allowed
Adverse effects of all prior systemic or local treatment must have either returned to baseline or become stable and manageable prior to initiation of study treatment.
Ocular melanoma
Leptomeningeal involvement
Uncontrolled tumour-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days.
Prior WBRT treatment for CNS disease
Increasing corticosteroid dose during the seven days prior to initiation of study treatment or current dexamethasone or equivalent dose of \> 8 mg/day
Prior treatment with a BRAF or MEK inhibitor
For patients assigned to Cohort 1 only: prior immunotherapy in the metastatic setting is not allowed. Prior immunotherapy is allowed in the adjuvant setting, provided it is completed ≥ 90 days prior to study treatment initiation.
For patients assigned to Cohort 2 only: prior immunotherapy in either the adjuvant or metastatic setting is not allowed.
Major surgical procedure other than for diagnosis within four weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or to any formulation component of cobimetinib or atezolizumab or, for patients assigned to Cohort 2 only, vemurafenib
Any anti-cancer therapy, including chemotherapy, hormonal therapy and radiotherapy, within two weeks prior to initiation of study treatment
Patients assigned to Cohort 2 only: Concomitant treatment with anticonvulsants other than gabapentin, vigabatrin and levetiracetam
Patients assigned to Cohort 2 only: acetaminophen is prohibited within seven days prior to initiation of study treatment unless the patient has an absolute contraindication to the to the use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin
Active malignancy (other than melanoma) or a prior malignancy within the past three years
Known risk factors for ocular toxicity
History of clinically significant cardiac dysfunction
Inability to swallow medications
Malabsorption condition that would alter the absorption of orally administered medications
Traumatic injury within two weeks prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplantation
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Uncontrolled diabetes or symptomatic hyperglycaemia
Any Grade ≥ 3 haemorrhage or bleeding event within 28 days of study treatment initiation
History of stroke, reversible ischemic neurological defect, or transient ischemic attack within six months prior to study treatment initiation
Positive human immunodeficiency virus (HIV) test at screening
Hepatitis B virus (HBV) infection (chronic or acute)
Active hepatitis C virus (HCV) infection
Active tuberculosis
History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Severe infection within four weeks prior to initiation of study treatment
Signs or symptoms of infection within two weeks prior to initiation of study treatment
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in, and completion of, the study
Any psychological, familial, sociological, or geographical condition that may hamper compliance with the protocol and follow-up after treatment discontinuation
Pregnancy, breastfeeding, or intention of becoming pregnant during the study. Women of childbearing potential must have a negative serum pregnancy test result within seven days prior to initiation of study treatment.
Treatment with therapeutic oral or IV antibiotics within two weeks prior to initiation of study treatment
Administration of a live, attenuated vaccine within four weeks prior to initiationof study treatment or anticipation of need for such a vaccine during the study
Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug, whichever is shorter, prior to study treatment initiation
Treatment with systemic immunosuppressive medications within two weeks prior to study treatment initiation
Treatment with investigational drug within 28 days or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
For patients to be assigned to Cohort 2 only: anticipated use of any concomitant medication during or within seven days prior to initiation of study treatment that is known to cause QT prolongation
Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least seven days prior to initiation of study treatment.
Clareo Health | A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases
