NCT02145910

Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases

Phase I Study of Vemurafenib Combined With Whole Brain Radiation Therapy (WBRT) or Radiosurgery (SRS) for Melanoma Patients With BRAF Mutation Presented With Brain Metastases

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the best dose of vemurafenib when combined with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) in patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation-positive melanoma and brain metastases. Radiation therapy is an effective treatment for patients with brain metastases. Patients with multiple metastases are typically treated with WBRT. For patients with a few metastases, SRS alone can be used. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Combining radiation treatment with vemurafenib for melanoma patients with brain metastases may result in improved local control and prolonged survival.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of vemurafenib when combined with WBRT or SRS and determine a recommended phase II dose of vemurafenib to be used with WBRT or SRS in patients with brain metastases from melanoma. SECONDARY OBJECTIVES: I. To determine local control rates of the brain metastases in each arm. II. To determine the rates of developing of new brain metastases in each arm. III. To determine the response of extracranial disease. IV. To determine the overall survival rate and progression free survival rate. V. To determine the safety and tolerability of each arm. OUTLINE: This is a dose-escalation study of vemurafenib. Patients are assigned to 1 of 2 arms based on the number and size of brain metastasis. All patients receive vemurafenib orally (PO) twice daily (BID) beginning 3-5 days before the start of radiation therapy and continuing in the absence of disease progression or unacceptable toxicity. ARM A: Patients undergo WBRT once daily (QD) for 10 doses. ARM B: Patients undergo SRS (gamma knife, tomotherapy, cyberknife, or megavoltage linear accelerator \[LINAC\] radiation therapy) on day 1. After completion of study therapy, patients are followed up on weeks 5 or 7, 9 and 13, and then on months 4, 6, 9, and 12.

Conditions

• Recurrent Melanoma
• Stage IV Melanoma
• Tumors Metastatic to Brain

Interventions

Type	Name	Description
DRUG	Vemurafenib	Given PO
RADIATION	Whole-brain radiation therapy (WBRT)	Undergo WBRT
RADIATION	Radiosurgery (SRS)	Undergo SRS

Timeline

• Primary completion: 2019-06-01
• First posted: 2014-05-23
• Last updated: 2025-05-02