Clinical trial NCT00837928: Bendamustine and 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
tumors metastatic to brain
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
First posted: 2009-02-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Determine recommended dose of Bendamustine when used in combination with Stereotactic Radiotherapy (STR) for treatment of patients with 1-4 brain metastases.
timeFrame: up to 4 years
Secondary outcomes:
measure: Pharmacokinetics of bendamustine
timeFrame: up to 4 years
measure: Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma
timeFrame: up to 4 years
measure: Local control of brain metastases
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: John C. Grecula, MD
role: PRINCIPAL_INVESTIGATOR
References: