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

Condition(s) targeted: Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: bendamustine (Drug); laboratory biomarker analysis (Other); therapeutic conventional surgery (Procedure); stereotactic body radiation therapy (Radiation)

Phase: Phase 1

Status: Recruiting

Sponsored by: Ohio State University Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
John C. Grecula, MD, Principal Investigator, Affiliation: Ohio State University

Overall contact:
Ohio State University Comprehensive Cancer Center, Phone: 1-800-293-5066, Email: Jamesline@osumc.edu

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.

Official title: Phase I Study of Bendamustine and Fractionated Stereotactic Radiotherapy of Patients With 1- 4 Brain Metastases From Solid Malignancies

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Determine recommended dose of Bendamustine when used in combination with Stereotactic Radiotherapy (STR) for treatment of patients with 1-4 brain metastases.

Secondary outcome:

Pharmacokinetics of bendamustine

Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma

Local control of brain metastases

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 1-3 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Ohio State University Comprehensive Cancer Center, Phone: 1-800-293-5066, Email: Jamesline@osumc.edu

Ohio State University Medical Center, Columbus, Ohio 43210, United States; Recruiting
John Grecula, MD, Phone: 614-293-8415, Email: John.Grecula@osumc.edu

Jamesline

Starting date: February 2009
Last updated: March 2, 2012