Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific, tumors metastatic to brain
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.
Interventions
DRUGbendamustine
40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.
OTHERlaboratory 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).
PROCEDURESurgical Resection of Brain Metastases
Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)
RADIATIONStereotactic body radiation therapy
Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)
Sponsors
National Comprehensive Cancer Network
John Grecula
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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. | up to 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of bendamustine | up to 4 years |
| Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma | up to 4 years |
| Local control of brain metastases | up to 4 years |
Countries
United States
Outcome results
None listed