- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00837928
Bendamustine and Radiation Therapy in Treating Patients With Brain Metastases Caused by Solid Tumors
Phase I Study of Bendamustine and Fractionated Stereotactic Radiotherapy of Patients With 1- 4 Brain Metastases From Solid Malignancies
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.
Study Overview
Status
Detailed Description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed cancer with 1 to 4 brain metastases imaged by MRI/CT scans not involving thalamus, basal ganglia or brain stem.
- No cancer originating in central nervous system
- Candidate for clinically indicated surgery to resect brain lesions.
- Karnofsky score of at least 60
- At least 18 years of age
- Life expectancy of more than two months
Exclusion Criteria:
- Evidence of leptomeningeal metastases.
- Need immediate treatment to prevent neurological deterioration.
- Prior brain radiotherapy or surgery for current brain metastases.
- Radiosensitive primary tumors such as small cell lung cancer, germ cell tumors, lymphoma, leukemia or multiple myeloma.
- Absolute neutrophil count (ANC)<1500/mm3 or platelets <50,000/mms.
- Brain metastasis diameter greater than 5 cm.
- Not pregnant or nursing
- More than 3 weeks since prior chemotherapy.
- No evidence of ischemia on EKG and/or reduced cardiac ejection fraction (i.e., < 50%) on ECHO.
- No known sensitivity or allergy to bendamustine hydrochloride or mannitol
- No more than 3 prior cytotoxic chemotherapy regimens
- No unresolved persistent toxicities for 4 weeks from prior chemotherapy or 6 weeks for nitrosoureas.
- Calculated creatinine clearance <40 ml/min.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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).
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40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.
Other Names:
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 Names:
Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)
Other Names:
Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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up to 4 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Pharmacokinetics of bendamustine
Time Frame: up to 4 years
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up to 4 years
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Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma
Time Frame: up to 4 years
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up to 4 years
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Local control of brain metastases
Time Frame: up to 4 years
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up to 4 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: John C. Grecula, MD, Ohio State University
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Bendamustine Hydrochloride
Other Study ID Numbers
- OSU-08142
- NCI-2011-03179 (Registry Identifier: Clinical Trial Reporting Program (CTRP))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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