Bendamustine and Radiation Therapy in Treating Patients With Brain Metastases Caused by Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.
PURPOSE: This phase I trial is studying the side effects and best dose of bendamustine when given together with radiation therapy in treating patients with brain metastases caused by solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Other: laboratory biomarker analysis
Procedure: Surgical Resection of Brain Metastases
Radiation: Stereotactic body radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Bendamustine and Fractionated Stereotactic Radiotherapy of Patients With 1- 4 Brain Metastases From Solid Malignancies|
- Determine recommended dose of Bendamustine when used in combination with Stereotactic Radiotherapy (STR) for treatment of patients with 1-4 brain metastases. [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of bendamustine [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Local control of brain metastases [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Bendamustine and Fractionated stereotactic radiotherapy
Bendamustine 40 mg/m2 and will be administered IV on days 1,2,and 3 prior to surgery on each day of SRT (Sterotactic radiation therapy). Laboratory biomarker analysis will be obtained on day 1 or 2 only from patients undergoing surgery on day 3 (i.e. Pharmacokinetic samples will not be collected from patients who begin SRT on day 1). Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine) Stereotactic fractionated radiation therapy starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri). Concurrent Bendamustine is administered on Days of Stereotactic Radiotherapy (Arm 1: 40 mg/m2/ Day; Arm 2: 50 mg/m2/day).
40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.
Other Names:Other: laboratory biomarker analysis
samples will be obtained on day 1 or 2 only from patients undergoing surgery on day 3 (i.e. PK samples will not be collected from patients who begin SRT on day 1).
Other Name: Laboratory ProcedureProcedure: Surgical Resection of Brain Metastases
Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)
Other Name: surgeryRadiation: Stereotactic body radiation therapy
Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)
- Determine the recommended phase II dose of bendamustine hydrochloride when administered in combination with stereotactic radiotherapy for the treatment of patients with 1-4 brain metastases from solid malignancies.
- Determine bendamustine hydrochloride pharmacokinetics and correlate this to bendamustine hydrochloride levels in brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma acquired at the time of surgery.
- Assessment of local control of brain metastases.
OUTLINE: This is a dose-escalation study of bendamustine hydrochloride.
Patients with no potentially resectable lesion(s) receive bendamustine hydrochloride IV over 30 minutes and stereotactic radiotherapy once daily for 5 days.
Patients with potentially resectable lesion(s) receive bendamustine hydrochloride IV over 30 minutes on days 1-3 and undergo surgery on day 3. At least 4 weeks after surgery, these patients receive adjuvant bendamustine hydrochloride and stereotactic fractionated radiotherapy as above (in patients with no potentially resectable lesion[s])
Blood samples are collected periodically for pharmacokinetic studies. Cerebrospinal fluid, arachnoid, tumor margin, and tumor samples are also collected during surgery for correlative studies.
After completion of study treatment, patients are followed every 3 months for 21 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00837928
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||John C. Grecula, MD||Ohio State University|