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

May 14, 2018 updated by: John Grecula

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 fractionated radiation therapy starting at least 4 weeks after surgery (Day 1 if no surgery ); 30 Gy in 5 daily fractions(Mon-Fri). Concurrent Bendamustine is administered on Days of Stereotactic Radiotherapy (Arm 1: 40 mg/m2/ Day; Arm 2: 50 mg/m2/day).
40 mg/m2 will be administered IV on days 1,2,and 3 prior to surgery.on each day of SRT.
Other Names:
  • Treanda
  • Ribomustin
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 Names:
  • Laboratory Procedure
Surgical Resection of Brain Metastases Day 3 (immediately after Bendamustine)
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome 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.
Time Frame: up to 4 years
up to 4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics of bendamustine
Time Frame: up to 4 years
up to 4 years
Levels of bendamustine hydrochloride in the brain metastases, brain margin, arachnoid, cerebral spinal fluid, and plasma
Time Frame: up to 4 years
up to 4 years
Local control of brain metastases
Time Frame: up to 4 years
up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: John C. Grecula, MD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 19, 2009

Primary Completion (Actual)

January 8, 2015

Study Completion (Actual)

January 8, 2015

Study Registration Dates

First Submitted

February 5, 2009

First Submitted That Met QC Criteria

February 5, 2009

First Posted (Estimate)

February 6, 2009

Study Record Updates

Last Update Posted (Actual)

May 17, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

May 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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