Status:
TERMINATED
Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases
Lead Sponsor:
Melissa Burgess, MD
Collaborating Sponsors:
Genentech, Inc.
Conditions:
Active Melanoma Brain Metastases
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
The purpose of this study is to evaluate the effectiveness of the combination of vemurafenib with cobimetinib in patients with active melanoma brain metastases.
Eligibility Criteria
Inclusion
- Signed informed consent
- Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600-mutation
- Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
- At least one measurable intracranial target lesion for which all of the following criteria are met:
- previously untreated or progressive according to RECIST 1.1 (equal to or greater than 20% increase in longest diameter on baseline scan) after previous local therapy (SRS and/or craniotomy)
- immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy (SRS and/or craniotomy)
- largest diameter of ≥ 0.5cm but ≤ 4 cm as determined by contrast-enhanced MRI
- Prior therapies for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy will be allowed but prior BRAF or MEK not allowed
- ECOG PS 0-2
- Life expectancy \>12 weeks
- Age 18 years or older
- Adequate bone marrow function as indicated by the following:
- ANC \> 1500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin \> 9 g/dL
- Adequate renal function, as indicated by creatinine =/\< 1.5 x the upper limit of normal (ULN)
- Adequate liver function, as indicated by bilirubin =/\< 1.5 x ULN
- AST or ALT \< 3 x ULN (patients with documented liver metastases: AST and/or ALT =/\< 5 x ULN)
- Able to swallow pills
- Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year
- Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
Exclusion
- Active infection
- Prior therapy with BRAFi and/or MEKi
- Leptomeningeal disease
- Symptomatic brain metastases requiring immediate local interventions such as craniotomy or SRS
- Increasing corticosteroid dose in 7 days prior to administration of first dose of study drug. Symptomatic patients that have stable or decreasing corticosteroid use in the past 7 days will be allowed
- Current use of therapeutic warfarin
- Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) \[NCI, 2009\] Grade 2 or higher from previous anti-cancer therapy, except alopecia
- Conditions that will interfere significantly with the absorption of drugs
- Inability to undergo MRI secondary to metal, claustrophobia, Gadolinium Contrast allergy
- Pregnant, lactating, or breast feeding women
- Prior radiation therapy within the last 14 days
- Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Unwillingness or inability to comply with study and follow-up procedures
- The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:
- St. John's wort or hyperforin
- Grapefruit juice
- History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, Retinal Vein Occlusion (RVO), or neovascular macular degeneration
- Uncontrolled glaucoma with intra-ocular pressures \> 21mmHg
- Serum cholesterol ≥ Grade 2
- Hypertriglyceridemia ≥ Grade 2
- Hyperglycemia (fasting) ≥ Grade 2
- History of clinically significant cardiac dysfunction, including the following:
- Current unstable angina
- Current symptomatic congestive heart failure of NYHA class 2 or higher
- History of congenital long QT syndrome or mean QTcF \> 450 msec at baseline or uncorrectable electrolyte abnormalities
- Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 1 are eligible)
- Left ventricular ejection fraction (LVEF) below 50%
- Uncontrolled Arrhythmias
- Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months
Key Trial Info
Start Date :
February 1 2015
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2016
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT02230306
Start Date
February 1 2015
End Date
March 1 2016
Last Update
October 12 2017
Active Locations (6)
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1
Harriet Kluger
New Haven, Connecticut, United States, 06510
2
Mohammed Milhem, MD
Iowa City, Iowa, United States, 52242
3
Anna Pavlick, MD
New York, New York, United States, 10016
4
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065