Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Nervous System Diseases

Rare Diseases

Neoplasm Metastasis

Recurrence

Melanoma

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients undergo WBRT once daily (QD) for 10 doses

Patients undergo SRS (gamma knife, tomotherapy, cyberknife, or megavoltage LINAC radiation therapy) on day 1

Whole-brain radiation therapy (WBRT)

Radiosurgery (SRS)

Wenyin Shi, MD, PhD

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.

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.

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

The last dose studied or the previous dose, based on clinical judgment of the degree of toxicity seen at the last dose.

Estimate through the Kaplan-Meier method and compute associated 95% confidence intervals

Will be determined for each arm separately, as well as the entire study patient population

Analysis of local control will be done separately in each arm

Analysis of rate of developing new brain metastasis will be done separately in each arm

Genentech, Inc.

Sidney Kimmel Cancer Center at Thomas Jefferson University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases	NCT02145910	Recurrent Melan... Stage IV Melano... Tumors Metastat...	Vemurafenib Whole-brain rad... Radiosurgery (S...	18 Years -	Thomas Jefferson University
Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases	NCT02145910	Recurrent Melan... Stage IV Melano... Tumors Metastat...	Vemurafenib Whole-brain rad... Radiosurgery (S...	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for radiosurgery (srs)