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

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ClinicalTrials.gov Identifier: NCT02427893
Recruitment Status : Withdrawn (no patients were enrolled)
First Posted : April 28, 2015
Last Update Posted : November 15, 2016
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Cobimetinib Drug: Vemurafenib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : August 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Cohort 1
Ten patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.
Drug: Cobimetinib
A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.
Other Name: GDC-0973, XL518
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
Other Name: RO5185426, PLX4032, or RG7204
Active Comparator: Cohort 2
Ten patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.
Drug: Cobimetinib
A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.
Other Name: GDC-0973, XL518
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
Other Name: RO5185426, PLX4032, or RG7204



Primary Outcome Measures :
  1. Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma. [ Time Frame: 2 years ]
    compare immunologic changes described above with the development of study treatment-related adverse events. For example, severity or extent of rash from cobimetinib (a well-described dermatologic toxicity of MEK inhibitors) may be compared to levels of intratumoral immune activation assessed by one or more of the parameters.


Secondary Outcome Measures :
  1. Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma. [ Time Frame: 2 years ]
    compare immunologic changes described above with therapeutic outcomes, including CR, PR, SD, and PD measured by RECIST 1.1. For example, tumor regression may be correlated with levels of intratumoral immune activation or expression of immune checkpoints assessed by one or more of the parameters



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427893


Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Genentech, Inc.
Investigators
Principal Investigator: Evan J Lipson, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02427893     History of Changes
Other Study ID Numbers: J1517
IRB00051085 ( Other Identifier: JHMIRB )
First Posted: April 28, 2015    Key Record Dates
Last Update Posted: November 15, 2016
Last Verified: November 2016

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
immunotherapy
Vemurafenib
Cobimetinib

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Vemurafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action