The Effects of Vemurafenib + Cobimetinib on Immunity in Patients With Melanoma

Description

This study is for patients with malignant melanoma which has spread beyond the local area and cannot be surgically removed, and who have melanoma tumors that are accessible for repeat biopsies. This research study is a way of gaining new knowledge about treatment options for metastatic melanoma. This research study is evaluating the effects of a drug called vemurafenib on the immune system. Vemurafenib has been approved by the FDA for treatment of patients with advanced melanoma that harbors a B-RAF mutation. Vemurafenib works by blocking a protein called B-RAF. Researchers have found that a large number of melanomas have mutations (changes) in the BRAF gene. Genes are specific parts of your DNA that contain information on hereditary characteristics such as hair color and eye color. The BRAF gene codes for a protein called B-RAF, which is involved in sending signals in cells that can lead to cell growth. Research has determined that mutations in the BRAF gene at the V600 position cause a change in the B-RAF protein that can drive the growth and spread of melanoma cells. The purpose of this research study is to determine how vemurafenib may alter the immune system's reaction to melanoma, in order to learn how best to combine immune therapies with vemurafenib in the future.

Study Start Date

March 2013

Estimated Completion Date

December 2016

Interventions

  • Drug: Vemurafenib

Specialties

  • Oncology: Dermatologic Oncology,Pharmacology/Therapy
  • Allergy/Immunology: Clinical Pharmacology,Hematology/Oncology

MeSH Terms

  • Immunity
  • Melanoma
  • Vemurafenib

Study ID

Georgetown University -- MLN28305

Status

Unknown

Trial ID

NCT01813214

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

15

Sponsor

Georgetown University

Inclusion Criteria

  • Patients must have histological or cytological confirmed melanoma that is metastatic or unresectable stage IIIc and clearly progressive.
  • Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
  • Age >/= 18 years
  • ECOG performance status 0, 1, or 2
  • Participants must have measurable melanoma
  • Women must not be pregnant
  • Breastfeeding must be discontinued prior to treatment Day 1 of the study.
  • Subjects may have received any number of prior systemic treatment regimens for distant metastatic disease or advanced regional disease. The following prior therapy is permitted in either the adjuvant or metastatic disease setting:
  • No prior therapy
  • Immunotherapy consisting of interferon-alpha, interleukin-2, GM-CSF, ipilimumab, anti-PD1, cancer vaccines, or other experimental agent
  • Cytotoxic chemotherapy consisting of dacarbazine, temozolomide, carboplatin, or paclitaxel alone or in combination
  • Targeted therapy with temsirolimus, bevacizumab, or sorafenib
  • Subjects must have discontinued cytotoxic therapy agents at least 4 weeks, cytokine based immunotherapy at least 6 weeks and immunoregulatory antibody therapy at least 12 weeks prior to entering the study and have recovered from adverse events due to those agents.
  • Subjects must have completed radiation therapy at least 4 weeks previously
  • Subjects must have the following baseline laboratory values:
  • White blood count >/= 3000/mm3
  • Absolute granulocyte count >/= 1500/mm3
  • Platelet count >/= 100,000/mm3
  • Serum creatinine /= 40 ml/min
  • AST/ALT
  • Alkaline Phosphatase
  • INR
  • Total bilirubin
  • Subjects must not receive any other investigational agents during the period on study or the four weeks prior to entry.
  • Subjects must have no clinical evidence of active brain metastasis.
  • Subjects who have had brain metastases will be eligible only if all of the following are true:
  • The total number of brain metastases ever is
  • All are less than or equal to 2 cm
  • They have been resected surgically or have been treated with gamma-knife or stereotactic radiosurgery
  • The patient has not taken any steroids
  • Subjects must not have a serious intercurrent illness including, but not limited to:
  • Ongoing or active infection requiring parenteral antibiotics on Day 1
  • History of congenital long QT syndrome or mean corrected QTc interval > 450 msec at baseline
  • Clinically significant cardiovascular disease: i. Myocardial infarction within 6 months ii. Unstable angina iii. New York heart association grade II or greater congestive heart failure iv. Serious cardiac arrhythmia requiring medication
  • Serious non-healing wound, active ulcer, or untreated bone fracture
  • Psychiatric illness/ social situations that would limit compliance with study requirements.
  • Subjects must be HIV negative
  • Subjects must be Hepatitis C negative
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Prior therapy with a MEK inhibitor or an inhibitor of mutant BRAF
  • Patients on warfarin therapy due to the requirement for multiple biopsies
  • Subjects who have another cancer diagnosis, except that the following diagnoses will be allowed:
  • Squamous cell cancer of the skin without known metastasis. Subjects with suspected cuSCCs should have them excised prior to study registration
  • Basal cell cancer of the skin without known metastasis
  • Carcinoma in situ of the breast (DCIS or LCIS)
  • Carcinoma in situ of the cervix
  • Any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis over 3 years

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (4)

Study Location Distance Name Phone Email
Massachusetts General Hospital - Boston, Massachusetts 2.8 miles Haley Garbus None HGARBUS@MGH.HARVARD.EDU
Georgetown Lombardi Comprehsnive Cancer Center - Washington, District of Columbia 394.4 miles Bridget Haley BSN 202-687-6871 BLH50@georgetown.edu
University of Virginia Health System - Charlottesville, Virginia 493.5 miles Sarah Kelley 434-982-6584 slk6vj@virginia.edu
University of Texas MD Anderson Cancer Center - Houston, Texas 1,609.9 miles Donna Branham RN 713-563-3527 dbranham@mdanderson.org

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