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

Melanoma Clinical Trial

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02427893
• Other study ID #: J1517
• Secondary ID: IRB00051085
• Status: Withdrawn
• Phase: Phase 3
• First received: March 27, 2015
• Last updated: November 14, 2016
• Start date: August 2015
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

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

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.	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.	2 years	No
Secondary	Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.	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	2 years	No