test

Phase II neoadjuvant vemurafenib trial in melanoma patients with untreated brain metastases with B-raf mutations

Conditions

Cancer | Melanoma, skin

Trial Phase

Phase II

Trial Purpose and Description

Trial Purpose

Primary Objectives/Endpoints:

  • To determine the brain metastasis response rate in patients treated with vemurafenib prior to local therapy (LITT, SRS or resection).
  • To evaluate tumor BBB passage of vemurafenib in a subset of patients, as determined by levels of drug in brain metastases and levels of pERK in tumor.


Participation Guidelines

Age:
18 Years and older
Gender:
Both

Eligibility Criteria

Inclusion Criteria:

  • Biopsy proven metastatic melanoma with the B-raf V600E or V600K mutations.
  • Untreated brain metastases.
  • At least one cerebral metastasis that is not amenable to stereotactic radiosurgery (SRS) or surgical resection based on size or location OR four or more lesions.
  • Patients may be symptomatic at the time of enrollment, but after any necessary local therapy and/or corticosteroids, the patient should be asymptomatic when vemurafenib is initiated.
  • Age >18
  • Adequate organ function.
  • ECOG performance status < 3.
  • No prior therapies with selective inhibitors of mutated BRAF other prior therapies must have been administered at least 4 weeks before administration of vemurafenib.
  • Life expectancy of at least 3 months.
  • Understanding and willingness to consent.
  • The use of corticosteroids to control cerebral edema or treat symptoms will be allowed.
  • A history of whole brain radiotherapy for brain metastases is allowed, but any stable lesion that was present at the time of WBRT will NOT be considered evaluable. A minimum of 1 week break will be required between prior WBRT and initiation of vemurafenib therapy.

Exclusion Criteria:

  • Presence of leptomeningeal disease based on positive CSF cytology.
  • History or presence of clinically significant ventricular or atrial dysrhythmias &ge Grade 2 (NCI CTCAE, v4.0), Corrected QT (QTc) interval >450 ms at baseline or history of congenital long QT syndrome.
  • Uncontrolled medical illness, such as uncontrolled infection, congestive heart failure and MI within 2 months.
  • Second active, untreated malignancy, which is likely to result in the patient&rsquos demise prior to death from uncontrolled melanoma CNS metastases. This will be determined on a case by case basis by the PIs.
  • Unwillingness to undergo monitoring for a secondary malignancy including clinical dermatologic examinations and head and neck examinations and serial CT scans.

Sponsor:
Genentech, Inc.
Dates:
08/07/2013
Last Updated:
Study HIC#:
1208010666