Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases

NCT02230306 | Terminated Phase 2 Results DMC

• 2 other identifiers: 13-123ML29155
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the effectiveness of the combination of vemurafenib with cobimetinib in patients with active melanoma brain metastases.

Conditions

Active Melanoma Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Objective Intracranial Response (OIRR)

  Change in overall size of the sum of diameters from baseline of up to 5 intracranial target lesions in response to study treatment, achieved by individual patients.

  Until disease progression, less than or equal to 5 years.

Secondary Outcomes (7)

• Overall Response

  Until disease progression, less than or equal to 5 years.

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• Duration of Response

  Until disease progression, less than or equal to 5 years.

• Immune Modulation in Peripheral Blood

  Up to 5 years

Study Arms (1)

Cobimetinib in Combination with Vemurafenib

EXPERIMENTAL

Vemurafenib (960 mg twice a day) will be taken on Days 1 - 28 of each 28-day treatment cycle. The first dose of vemurafenib should be taken in the morning, and the second dose should be taken in the evening. Vemurafenib can be taken with or without a meal and should be taken with a glass of water. Cobimetinib (60 mg once a day) will be taken on Days 1 - 21 of each 28-day treatment cycle. The cobimetinib tablet should be taken at approximately the same time each day in the morning with the vemurafenib dose, but no later than 4 hours after the scheduled time. Cobimetinib can be taken with or without a meal and should never be chewed, cut, or crushed and should be taken with a glass of water.

Drug: Cobimetinib; Drug: Vemurafenib

Interventions

Cobimetinib DRUG

60mg once a day; will be taken on days 1-21 of each 28 day treatment cycle; will be taken in combination with Vemurafenib;

Cobimetinib in Combination with Vemurafenib

Vemurafenib DRUG

960mg twice a day; 28 day treatment cycle; will be taken in combination with Cobimetinib;

Also known as: Zelboraf

Cobimetinib in Combination with Vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600-mutation
• Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
• At least one measurable intracranial target lesion for which all of the following criteria are met:
• previously untreated or progressive according to RECIST 1.1 (equal to or greater than 20% increase in longest diameter on baseline scan) after previous local therapy (SRS and/or craniotomy)
• immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy (SRS and/or craniotomy)
• largest diameter of ≥ 0.5cm but ≤ 4 cm as determined by contrast-enhanced MRI
• Prior therapies for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy will be allowed but prior BRAF or MEK not allowed
• ECOG PS 0-2
• Life expectancy \>12 weeks
• Age 18 years or older
• Adequate bone marrow function as indicated by the following:
• ANC \> 1500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin \> 9 g/dL

You may not qualify if:

• Active infection
• Prior therapy with BRAFi and/or MEKi
• Leptomeningeal disease
• Symptomatic brain metastases requiring immediate local interventions such as craniotomy or SRS
• Increasing corticosteroid dose in 7 days prior to administration of first dose of study drug. Symptomatic patients that have stable or decreasing corticosteroid use in the past 7 days will be allowed
• Current use of therapeutic warfarin
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) \[NCI, 2009\] Grade 2 or higher from previous anti-cancer therapy, except alopecia
• Conditions that will interfere significantly with the absorption of drugs
• Inability to undergo MRI secondary to metal, claustrophobia, Gadolinium Contrast allergy
• Pregnant, lactating, or breast feeding women
• Prior radiation therapy within the last 14 days
• Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Unwillingness or inability to comply with study and follow-up procedures
• The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:
• St. John's wort or hyperforin

Sponsors & Collaborators

• Melissa Burgess, MD: lead
• Genentech, Inc.: collaborator

Study Sites (6)

Harriet Kluger

New Haven, Connecticut, 06510, United States

Location

Mohammed Milhem, MD

Iowa City, Iowa, 52242, United States

Location

Anna Pavlick, MD

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ravi Amaravadi, MD

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

cobimetinib; Vemurafenib

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Melissa Burgess, MD
• Organization: University of Pittsburgh Cancer Institute

burgessma@upmc.edu

412-623-7277

Study Officials

• Melissa Burgess, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Richard Carvajal, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Anna Pavlick, MD

  NYU Clinical Cancer Center

  PRINCIPAL INVESTIGATOR

• Mohammed Milhem, MD

  Univ of Iowa

  PRINCIPAL INVESTIGATOR

• Ravi Amaravadi, MD

  Univ of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Harriet Kluger, MD

  Yale New Haven Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: September 3, 2014
• Study Start: February 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: October 12, 2017
• Results First Posted: October 12, 2017

Record last verified: 2017-09

Locations

US (6)