Clinical Trials /

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

NCT02427893

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: J1517
  • SECONDARY ID: IRB00051085
  • NCT ID: NCT02427893

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
CobimetinibGDC-0973, XL518Cohort 1
VemurafenibRO5185426, PLX4032, or RG7204Cohort 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1Active ComparatorTen patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.
  • Cobimetinib
  • Vemurafenib
Cohort 2Active ComparatorTen patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.
  • Cobimetinib
  • Vemurafenib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
Time Frame:2 years
Safety Issue:
Description: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

Measure:Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
Time Frame:2 years
Safety Issue:
Description: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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • immunotherapy
  • Vemurafenib
  • Cobimetinib

Last Updated

November 15, 2016