Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma

NCT ID: NCT02427893

Last Updated: 2016-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2016-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Melanoma

Keywords

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immunotherapy Vemurafenib Cobimetinib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

Ten patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.

Group Type ACTIVE_COMPARATOR

Cobimetinib

Intervention Type DRUG

A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.

Vemurafenib

Intervention Type DRUG

A low molecular weight, orally available inhibitor of the activated form of the BRAF serine-threonine kinase enzyme, which is commonly found in melanoma

Cohort 2

Ten patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.

Group Type ACTIVE_COMPARATOR

Cobimetinib

Intervention Type DRUG

A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.

Vemurafenib

Intervention Type DRUG

A low molecular weight, orally available inhibitor of the activated form of the BRAF serine-threonine kinase enzyme, which is commonly found in melanoma

Interventions

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Cobimetinib

A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.

Intervention Type DRUG

Vemurafenib

A low molecular weight, orally available inhibitor of the activated form of the BRAF serine-threonine kinase enzyme, which is commonly found in melanoma

Intervention Type DRUG

Other Intervention Names

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GDC-0973, XL518 RO5185426, PLX4032, or RG7204

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evan J Lipson, MD

Role: PRINCIPAL_INVESTIGATOR

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

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The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Countries

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United States

Other Identifiers

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IRB00051085

Identifier Type: OTHER

Identifier Source: secondary_id

J1517

Identifier Type: -

Identifier Source: org_study_id