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

NCT02145910 | Withdrawn Phase 1 DMC

• 3 other identifiers: 13P.4802013-025JT 2960
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Recurrent Melanoma; Stage IV Melanoma; Tumors Metastatic to Brain

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of vemurafenib

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

  Up to 1 year

Secondary Outcomes (8)

• Proportion with complete response

  Up to 1 year

• Proportion with partial response

  Up to 1 year

• Median survival

  Up to 1 year

• Progression free survival based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria based on the brain MRI and systematic assessment by the treating physician

  Up to 1 year

• Overall survival

  Up to 1 year

Study Arms (2)

WBRT + Vemurafenib

EXPERIMENTAL

Patients undergo WBRT once daily (QD) for 10 doses

Drug: Vemurafenib; Radiation: Whole-brain radiation therapy (WBRT)

SRS + Vemurafenib

EXPERIMENTAL

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

Drug: Vemurafenib; Radiation: Radiosurgery (SRS)

Interventions

Vemurafenib DRUG

Given PO

Also known as: Zelboraf

SRS + Vemurafenib; WBRT + Vemurafenib

Whole-brain radiation therapy (WBRT) RADIATION

Undergo WBRT

Also known as: WBRT, whole brain radiotherapy, whole-brain radiotherapy

WBRT + Vemurafenib

Radiosurgery (SRS) RADIATION

Undergo SRS

Also known as: Radiation surgery, SRS

SRS + Vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Histological confirmed melanoma (prior diagnosis okay)
• BRAFV600 mutation positive (cobas 4800 BRAFV600 mutation test)
• ECOG performance status 0 or 1
• Craniotomy resection is allowed (a minimum 2 weeks recovery time from surgery to initiation of protocol therapy)
• Radiographic evidence of brain metastasis
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• Adequate organ function:
• WBC ≥ 2000/uL
• ANC ≥ 1000/uL
• Platelets ≥ 75 x 103/uL
• Hemoglobin ≥ 9 g/dL (≥ 80 g/L; may be transfused)
• Creatinine ≤ 2.0 x ULN OR 24-hour creatinine clearance \>= 50 ml/min
• AST/ALT ≤ 2.5 x ULN for patients without liver metastasis, ≤ 5 times for liver metastases
• Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

You may not qualify if:

• Leptomeningeal involvement
• Cardiac disease: Congestive heart failure \> class II. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Pregnancy or breastfeeding
• Documented history of cranial hemorrhage
• Concurrent administration of any anticancer therapies other than those administered in the study
• Treatment with any cytotoxic, investigational drug, or targeted therapy within 2 weeks prior to the protocol treatment.
• Craniotomy within 2 weeks of protocol treatment.
• Prior treatment with other BRAF or MEK inhibitors
• Patients who had prior brain radiation. However, prior WBRT is allowed in Arm B.
• QTc \> 450 ms
• Patients have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated basal or squamous cell carcinoma of skin, superficial bladder cancer or carcinoma in situ of cervix, AJCC (version 7.0) stage 0 or I breast cancer, AJCC (version 7.0) stage I, or II prostate cancer.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Genentech, Inc.: collaborator

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Vemurafenib; Radiosurgery; Spermine Synthase

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Alkyl and Aryl Transferases; Transferases; Enzymes; Enzymes and Coenzymes

Study Officials

• Wenyin Shi, MD, PhD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 23, 2014
• Primary Completion: June 1, 2019
• Last Updated: May 2, 2025

Record last verified: 2025-05