Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM)
Sorafenib is a new type of anti-cancer drug. It belongs to a new class of medications known as tyrosine kinase inhibitors. Sorafenib is thought to work against cancer in many ways. It helps decrease blood supply to the tumor. It also blocks some proteins that help the tumor cells to grow." Sorafenib is approved by the Food and Drug administration (FDA) for treatment for other cancers like liver and kidney cancer. Sorafenib has also been studied in the treatment of breast cancer that has spread but is not specifically approved for the treatment of breast cancer. It has been studied both as a single agent and also in combination with other anti-cancer therapies for breast cancer. In laboratory models and in some patients with other cancers, sorafenib has been studied in tumors in the brain.
In this study, sorafenib will be given together with whole brain radiation therapy (WBRT). Overall this research study is designed to answer 2 main questions:
- What dose of sorafenib should be used together with WBRT?
- What are the side effects of sorafenib and WBRT when given together?
Radiation: Whole Brain Radiotherapy (WBRT)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM): A Phase I Study|
- Maximum Tolerated Dose [ Time Frame: 1 year ] [ Designated as safety issue: No ]Dose-escalation Phase: The proposed three dose levels of sorafenib during dose escalation are 200 mg, 400mg, and 600 mg administered daily orally. The dose-escalation phase is for 3-6 patients to be treated at each dose level. Assuming 3 dose levels during this phase, it will require a minimum of 2 and a maximum of 18 patients.
- assessing toxicity by the number of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]using the active version of the CTCAE version 4.0
- CNS progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]CNS-PFS is defined as the interval between the date of study entry and the date of intracranial tumor progression or death from any cause. We will evaluate this during follow-up MRI scans that will be performed as a standard of care using the Macdonald criteria.
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||November 2014|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Radiotherapy with Sorafenib
This is a single institution, open label, prospective, phase I clinical trial using standard 3+3 design. Histologically confirmed metastatic adenocarcinoma of the breast with radiologic evidence of new and/or progressive brain metastases (BM) with a clinical indication for WBRT will be enrolled.
Radiation: Whole Brain Radiotherapy (WBRT)
WBRT (30 Gy) will be delivered in 10 fractions. Standard opposed lateral fields with multifleaf collimation blocking will be used. Treatment will be administered on business days and delivered over an approximate 2 week period. Dexamethasone may be given at the discretion of the treating physician but the dose cannot exceed greater than 16mg daily as it is a strong CYP3A4 inducer. Patients will also receive a proton pump inhibitor with dexamethasone.Drug: Sorafenib
The proposed three dose levels of sorafenib during dose escalation are 200 mg, 400mg, and 600 mg administered daily orally. Patients will be enrolled in cohorts of 3.The first three subjects will take sorafenib 200 mg daily within a few hours after the first RT fraction. Sorafenib will be continued concurrently with WBRT (1 fraction /day x 10 fractions) without breaks and then continued after WBRTfor a total of 21 days. If no dose limiting toxicity (DLT) is observed in a cohort of 3 patients until two weeks after completion of WBRT, the next dose level will be evaluated.
|Contact: Andrew Seidman, MD||646-888-5445|
|Contact: Kathryn Beal, MD||212-639-5159|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Andrew Seidman, MD 646-888-5445|
|Contact: Kathryn Beal, MD 212-639-5159|
|Principal Investigator: Andrew Seidman, MD|
|Principal Investigator:||Andrew Seidman, MD||Memorial Sloan-Kettering Cancer Center|