Bendamustine and Radiation Therapy in Treating Patients With Brain Metastases Caused by Solid Tumors - Full Text View

Sponsor:	Ohio State University Comprehensive Cancer Center
Collaborator:	National Comprehensive Cancer Network
Information provided by (Responsible Party):	Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00837928

Purpose

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.

Condition	Intervention	Phase
Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: bendamustine Other: laboratory biomarker analysis Procedure: therapeutic conventional surgery Radiation: stereotactic body radiation therapy	Phase 1

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Bendamustine and Fractionated Stereotactic Radiotherapy of Patients With 1- 4 Brain Metastases From Solid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Bendamustine hydrochloride Bendamustine

U.S. FDA Resources

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:

Determine recommended dose of Bendamustine when used in combination with Stereotactic Radiotherapy (STR) for treatment of patients with 1-4 brain metastases. [ Time Frame: 2009-present ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of bendamustine [ Time Frame: 2009-present ] [ Designated as safety issue: No ]
Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma [ Time Frame: 2009-present ] [ Designated as safety issue: No ]
Local control of brain metastases [ Time Frame: 2009-present ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	February 2009
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Intervention Details:

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

Other Names:

Ribomustin
Treanda

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).

Other Name: Laboratory Procedure

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

Other Names:

Surgical resection
surgery

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

Other Names:

SRT
Stereotactic Fractionated Radiation Therapy

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00837928

Contacts

Contact: Ohio State University Comprehensive Cancer Center	1-800-293-5066	Jamesline@osumc.edu
Contact: John Grecula, MD	614-293-8415	John.Grecula@osumc.edu

Locations

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

Sponsors and Collaborators

Ohio State University Comprehensive Cancer Center

National Comprehensive Cancer Network

Investigators

Principal Investigator:

John C. Grecula, MD

Ohio State University

More Information

Additional Information:

Jamesline

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00837928 History of Changes
Other Study ID Numbers:	OSU-08142, NCI-2011-03179
Study First Received:	February 5, 2009
Last Updated:	March 2, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:

unspecified adult solid tumor, protocol specific
tumors metastatic to brain

Additional relevant MeSH terms:

Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Bendamustine
Nitrogen Mustard Compounds

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012