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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
John Grecula, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00837928
First received: February 5, 2009
Last updated: May 21, 2014
Last verified: May 2014
  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: Surgical Resection of Brain Metastases
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:


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: up to 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of bendamustine [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Local control of brain metastases [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: February 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine and Fractionated stereotactic radiotherapy
Bendamustine 40 mg/m2 and will be administered IV on days 1,2,and 3 prior to surgery on each day of SRT (Sterotactic radiation therapy). Laboratory biomarker analysis will be obtained on day 1 or 2 only from patients undergoing surgery on day 3 (i.e. Pharmacokinetic samples will not be collected from patients who begin SRT on day 1). Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine) Stereotactic body radiation therapy starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri).
Drug: bendamustine
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
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).
Other Name: Laboratory Procedure
Procedure: Surgical Resection of Brain Metastases
Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)
Other Name: surgery
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)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
John Grecula
National Comprehensive Cancer Network
Investigators
Principal Investigator: John C. Grecula, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: John Grecula, Principal Investigator, 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: May 21, 2014
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
Neoplastic Processes
Neoplasms
Pathologic Processes
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014