Clinical Trial Details
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[Information provided by: ClinicalTrials.gov, which provides patients, family members, and members of the public easy and free access to information on clinical studies for a wide range of diseases and conditions.]

NCT03430947 : Vemurafenib Plus Cobimetinib After Radiosurgery in Patients With BRAF-mutant Melanoma Brain Metastases
PhasePhase 2
AgesMin: 18 Years Max: N/A
Eligibility
Inclusion Criteria:

- Signed informed consent

- Female and male patients = 18 years of age

- Histologically confirmed metastatic melanoma (stage IV, per AJCC staging), carrying
BRAF V600-mutation

- Performed SRS within the last 14 days using a harmonized protocol in patients with at
least one measurable intracranial target lesion for which the following criteria are
met:

- Previously untreated (Lesions in previously irradiated area should not be
selected)

- Largest diameter of = 0.5 cm but = 4 cm as determined by contrast-enhanced MRI
and

- = 10 brain metastases

- ECOG performance status 0 - 2

- Life expectancy = 12 weeks

- Adequate bone marrow function as indicated by the following:

- ANC = 1500/µL

- Platelets = 100,000/µL and

- Hemoglobin = 9 g/dL

- Adequate renal function, as indicated by creatinine = 1.5 x ULN

- Adequate liver function, as indicated by bilirubin = 1.5 x ULN, AST or ALT = 3 x ULN
(documented liver metastases: AST and/or ALT = 5 x ULN)

- Adequate coagulation within 28 days prior to baseline visit

- Patients not receiving therapeutic anticoagulation: INR or aPTT = 1.5 x ULN

- patients receiving therapeutic anticoagulation: stable anticoagulation regimen
and stable INR

- Able to swallow pills

Exclusion Criteria:

- Symptomatic brain metastases requiring immediate local interventions such as
neurosurgery or radiosurgery

- Leptomeningeal disease (also synchronous with brain metastases)

- Prior therapy with BRAF or MEK inhibitors (prior therapies for metastatic melanoma
including chemo-, cytokine-, immuno-, biological and vaccine-therapy will be allowed)

- Prior whole brain irradiation (Patients with prior local therapy of brain metastases
are eligible)

- Requirement of more than 8 mg dexamethasone daily; patient should be stable on
steroids for 2 weeks

- Active and uncontrolled infection including HBV, HCV und HIV

- positive HIV test at screening

- Active hepatitis B virus (HBV) infection (chronic and acute), defined as having a
positive hepatitis B surface antigen (HBsAg) test at screening.

- Active hepatitis C virus (HCV) infection, defined as having a positive HCV
antibody test and positive HCV RNA test at screening

- Prior intra- or extracranial radiation therapy within the last 14 days prior to SRS

- Treatment with strong CYP3A4/5 inhibitors (e.g. ketoconazole) and inducers (e.g.
phenytoin, carbamazepine). The anticonvulsant levetiracetam is allowed but patient
should have been stable on levetiracetam for 2 weeks.

- 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 (e.g.
Colitis ulcerosa)

- Inability to undergo MRI secondary to:

- Metal

- Claustrophobia or

- Gadolinium contrast allergy

- 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

- Known hypersensitivity to any of the excipients of cobimetinib and vemurafenib

- The following foods/supplements are prohibited at least 7 days prior to initiation of
and during study treatment:

- St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)

- Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)

- Patient is included in another trial (non-interventional studies are allowed)

- Use of any investigational or non-registered product within the 30 days before patient
registration

- Woman of childbearing age with the exception they meet at least one of the following
criteria:

- Post-menopausal (no menses for 12 months w.o. an alternative medical cause or FSH
greater than 40 U/ml for 6 months)

- Sterilization (hysterectomy, bilateral salpingectomy, bilateral tubal occlusion
or bilateral oophorectomy)

- Consistently and correct application of contraceptives with a failure less than 1
% per year (defined as highly effective birth control method)

- Pregnant or lactating women

- Positive serum pregnancy test within 7 days prior to baseline visit. 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.

- 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

- Patients should be excluded if they have the following current conditions:

- Uncontrolled glaucoma with intra-ocular pressures > 21 mmHg,

- Serum cholesterol = Grade 2,

- Hypertriglyceridemia = Grade 2, or

- Hyperglycemia (fasting) = Grade 2

- History of clinically significant cardiac dysfunction, including the following:

- Myocardial infarction,

- Severe/unstable angina pectoris,

- Symptomatic congestive heart failure (NYHA stage = 2),

- cerebrovascular accident or transient ischemic attack within the previous 6
months,

- History of congenital long QT syndrome or mean QTcF > 450 msec 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) < 50%, or

- Uncontrolled arrhythmias
LinksPermanent Link to THIS page: https://virtualtrials.com/nct/display1trial.cfm?nct=NCT03430947      |      Link to official Clinicaltrials.gov listing
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