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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00837928
• Other study ID #: OSU-08142
• Secondary ID: NCI-2011-03179
• Status: Completed
• Phase: Phase 1
• Start date: February 19, 2009
• Est. completion date: January 8, 2015

Study information

• Verified date: May 2018
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 8, 2015
• Est. primary completion date: January 8, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

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

Other:
• 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).

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

Radiation:
• Stereotactic body radiation therapy
Starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri)

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
John Grecula	National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics of bendamustine		up to 4 years
Secondary	Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma		up to 4 years
Secondary	Local control of brain metastases		up to 4 years

External Links

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