Clinical trial NCT02427893: Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma
Official title: An Exploratory Study of the Immunological Effects of Vemurafenib and Cobimetinib, Administered Alone and in Combination, in Subjects With Advanced BRAF V600E/K Mutant Melanoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Melanoma
Keywords: immunotherapy
Vemurafenib
Cobimetinib
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2015-04-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial explores the immunologic effects of vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor), administered alone and in combination, to patients with advanced BRAF V600E/K mutant melanoma.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Signed HIV testing consent
* Life expectancy ≥ 12 weeks
* Able to swallow pills
* ECOG performance status 2 or less
* Adequate bone marrow function
* Adequate renal function
* Adequate liver function
* Negative urine pregnancy test within 7 days prior to commencement of dosing in premenopausal women
* Histological diagnosis of unresectable AJCC stage III or stage IV, BRAFV600E/K mutant melanoma
* Measurable disease
* Accessible tumor that can be biopsied
* Naive to targeted therapy (Prior immune-based therapy in the adjuvant setting or for advanced disease will be allowed if \>2 weeks from study entry)

Exclusion Criteria:

* Active systemic infection
* Active autoimmune disease or history of known or suspected autoimmune disease
* Active brain metastases or leptomeningeal metastases
* Treatment with any immunomodulatory medication within 4 weeks of initiation of study therapy.
* Positive test for hepatitis B virus
* Positive test for hepatitis C virus
* Positive test for human immunodeficiency virus (HIV)
* Pregnant, lactating or breast feeding women
* Localized radiation therapy within the last 14 days
* History of malabsorption
* No consumption of the following within 7 days prior to start of treatment:

  * St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
  * Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor
* History or evidence of cardiovascular risk
* History or evidence of retinal pathology

Primary outcomes:
measure: Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
timeFrame: 2 years
Secondary outcomes:
measure: Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Evan J Lipson, MD
role: PRINCIPAL_INVESTIGATOR
References: