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

Johns Hopkins Medicine

Status and phase: Withdrawn; Phase 3

Conditions: Melanoma

Treatments: Drug: Vemurafenib; Drug: Cobimetinib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02427893

J1517

IRB00051085 (Other Identifier)

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Cohort 1

Active Comparator group

Description:

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

Treatment:

Drug: Cobimetinib

Drug: Vemurafenib

Cohort 2

Active Comparator group

Description:

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

Treatment:

Drug: Cobimetinib

Drug: Vemurafenib