Bendamustine and Radiation Therapy in Treating Patients With Brain Metastases Caused by Solid Tumors

NCT ID: NCT00837928

Last Updated: 2018-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-19
• Study Completion Date: 2015-01-08

Brief Summary

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.

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.

Conditions

Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

bendamustine

Intervention Type: DRUG

40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.

laboratory biomarker analysis

Intervention Type: OTHER

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).

Surgical Resection of Brain Metastases

Intervention Type: PROCEDURE

Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)

Stereotactic body radiation therapy

Intervention Type: RADIATION

Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)

Interventions

bendamustine

40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.

Intervention Type: DRUG

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).

Intervention Type: OTHER

Surgical Resection of Brain Metastases

Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)

Intervention Type: PROCEDURE

Stereotactic body radiation therapy

Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)

Intervention Type: RADIATION

Other Intervention Names

Ribomustin; Treanda; Laboratory Procedure; surgery; SRT; Stereotactic Fractionated Radiation Therapy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

John Grecula

OTHER

Sponsor Role: lead

Responsible Party

John Grecula

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John C. Grecula, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Related Links

http://cancer.osu.edu

Jamesline

Other Identifiers

NCI-2011-03179

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-08142

Identifier Type: -

Identifier Source: org_study_id