NCT02427893

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Aug 2015

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 27, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 28, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

August 1, 2015

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

November 15, 2016

Status Verified

November 1, 2016

Enrollment Period

1.3 years

First QC Date

March 27, 2015

Last Update Submit

November 14, 2016

Conditions

Melanoma

Keywords

immunotherapyVemurafenibCobimetinib

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Anti-tumor activity of cobimetinib monotherapy and combination vemurafenib/cobimetinib in subjects with advanced melanoma.

    2 years

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

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

Drug: CobimetinibDrug: Vemurafenib

Cohort 2

ACTIVE COMPARATOR

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

Drug: CobimetinibDrug: Vemurafenib

Interventions

CobimetinibDRUG

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

Also known as: GDC-0973, XL518
Cohort 1Cohort 2
VemurafenibDRUG

A low molecular weight, orally available inhibitor of the activated form of the BRAF serine-threonine kinase enzyme, which is commonly found in melanoma

Also known as: RO5185426, PLX4032, or RG7204
Cohort 1Cohort 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

cobimetinibVemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Evan J Lipson, MD

    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 27, 2015

First Posted

April 28, 2015

Study Start

August 1, 2015

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

November 15, 2016

Record last verified: 2016-11

Locations

US(1)