Phase II neoadjuvant vemurafenib trial in melanoma patients with untreated brain metastases with B-raf mutations
Trial Purpose and Description
- 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.
- 18 Years and older
- 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.
- 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.
- Genentech, Inc.
- Last Updated:
- Study HIC#: