search
Back to results

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

Primary Purpose

Melanoma

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cobimetinib
Vemurafenib
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring immunotherapy, Vemurafenib, Cobimetinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Cohort 1

Cohort 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
March 27, 2015
Last Updated
November 14, 2016
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Genentech, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02427893
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Withdrawn
Why Stopped
no patients were enrolled
Study Start Date
August 2015 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
immunotherapy, Vemurafenib, Cobimetinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Active Comparator
Arm Description
Ten patients begin Vemurafenib monotherapy, after 10 days, begin combination therapy by adding Cobimetinib.
Arm Title
Cohort 2
Arm Type
Active Comparator
Arm Description
Ten patients begin Cobimetinib monotherapy, after 10 days, begin combination therapy by adding Vemurafenib.
Intervention Type
Drug
Intervention Name(s)
Cobimetinib
Other Intervention Name(s)
GDC-0973, XL518
Intervention Description
A potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Other Intervention Name(s)
RO5185426, PLX4032, or RG7204
Intervention Description
A low molecular weight, orally available inhibitor of the activated form of the BRAF serine-threonine kinase enzyme, which is commonly found in melanoma
Primary Outcome Measure Information:
Title
Safety and tolerability of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.
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
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evan J Lipson, MD
Organizational Affiliation
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs