Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM)
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|ClinicalTrials.gov Identifier: NCT01724606|
Recruitment Status : Active, not recruiting
First Posted : November 12, 2012
Last Update Posted : October 29, 2019
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?
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Brain Metastases||Radiation: Whole Brain Radiotherapy (WBRT) Drug: Sorafenib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM): A Phase I Study|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||November 2021|
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 multileaf 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.
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.
- Maximum Tolerated Dose [ Time Frame: 1 year ]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 ]using the active version of the CTCAE version 4.0
- CNS progression-free survival [ Time Frame: 1 year ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01724606
|United States, New Jersey|
|Memoral Sloan Kettering Cancer Center|
|Basking Ridge, New Jersey, United States|
|Memorial Sloan Kettering Monmouth|
|Middletown, New Jersey, United States, 07748|
|United States, New York|
|Memorial Sloan Kettering Cancer Center @ Suffolk|
|Commack, New York, United States, 11725|
|Memorial Sloan Kettering Westchester|
|Harrison, New York, United States, 10604|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Memorial Sloan Kettering Nassau|
|Uniondale, New York, United States, 11553|
|Principal Investigator:||Andrew Seidman, MD||Memorial Sloan Kettering Cancer Center|