Bendamustine in Treating Patients With Recurrent or Progressive Anaplastic Glioma or Glioblastoma Multiforme

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: bendamustine hydrochloride (Drug); quality-of-life assessment (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Marc C. Chamberlain, MD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Marc C. Chamberlain, MD, Study Chair, Affiliation: Fred Hutchinson Cancer Research Center

RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well bendamustine works in treating patients with recurrent or progressive anaplastic glioma or glioblastoma multiforme.

Official title: A Phase II Study of Bendamustine in the Treatment of Recurrent High-Grade Gliomas (Anaplastic Gliomas and Glioblastoma)

Study design: Treatment, Open Label

Primary outcome: Progression-free survival (PFS) at 6 months

Secondary outcome:

Best overall response over 12 months

PFS

Overall survival

Toxicity that results in significant reduction in or cessation of bendamustine treatment

Toxic death

Detailed description: OBJECTIVES:

Primary

- To determine the 6-month progression-free survival (PFS) in patients with recurrent or

progressive anaplastic glioma or glioblastoma multiforme treated with bendamustine hydrochloride.

Secondary

- To determine the safety of single agent bendamustine hydrochloride in these patients.

- To determine the efficacy of single agent bendamustine hydrochloride as assessed by the

6-month PFS of these patients.

- To assess quality of life of these patients using the FACT-BR.

OUTLINE: This is a multicenter study.

Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires (FACT-BR) at baseline and prior to each course.

After completion of study treatment, patients are followed at 1 month and then every 2 months for up to 3 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed supratentorial gliomas of the following subtypes:

- Anaplastic glioma

- Glioblastoma multiforme

- Must show unequivocal evidence for tumor recurrence or progression by MRI or CT scan

with contrast

- Must be in first or second recurrence

- Recent resection of recurrent or progressive tumor allowed, provided the following

criteria are met:

- More than 2 weeks since prior surgery and recovered

- Evaluable or measurable disease following resection

- Enhanced MRI or CT scan performed no later than 96 hours before and after surgery

or at least 4-6 weeks after surgery

- Must have failed prior external beam radiotherapy

- A PET or thallium single photon emission computed tomography (SPECT), magnetic

resonance spectroscopy (MRS) and magnetic resonance (MR) perfusion, or surgical documentation may be done at the discretion of the treating physician if there is a question of radiation changes or necrosis rather than progressive disease

- Patients who have undergone interstitial brachytherapy or stereotactic

radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or thallium SPECT, MRS and MR perfusion, or surgical documentation of disease

- Must have received ≥ 1 prior chemotherapy regimen that included temozolomide and no

more than 1 prior salvage chemotherapy

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy > 11 weeks

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 10 mg/dL (transfusion allowed)

- SGOT and SGPT < 3 times upper limit of normal (ULN)

- Bilirubin < 1. 5 times ULN

- Serum creatinine < 1. 5 mg/dL

- Glomerular filtration rate and creatinine clearance ≥ 30 mL/min

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No significant medical illnesses that, in the investigator's opinion, cannot be

adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

- No other cancer within the past 3 years except nonmelanoma skin cancer or carcinoma in

situ of the cervix, unless in complete remission and off of all therapy for that disease

- No known sensitivity to bendamustine hydrochloride or mannitol

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy

- At least 1 week since prior non-cytotoxic agents (e. g., interferon, tamoxifen,

thalidomide, cis-retinoic acid), except radiosensitizers

- At least 2 weeks since prior vincristine

- At least 3 weeks since prior procarbazine

- At least 4 weeks since prior cytotoxic therapy (6 weeks since prior nitrosoureas)

- At least 4 weeks since prior experimental biologic agents (e. g., EGFR inhibitors)

- At least 3 months since prior Gliadel implantation

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent enzyme-inducing anticonvulsants (non-enzyme-inducing anticonvulsants

allowed)

- No concurrent cytochrome CYP450 CYP1A2 pathway inhibiting or inducing agents (e. g.,

cimetidine, antidepressants, or antibiotics)

- No concurrent participation in another clinical trial

- No concurrent sargramostim (GM-CSF)

- No other concurrent anticancer therapy (i. e., chemotherapy, radiotherapy, hormonal

treatment, or immunotherapy)

- No other concurrent investigational drugs

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, United States; Recruiting
Lynn S. Ashby, MD, Phone: 602-406-6262, Email: lashby@chw.edu

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting
Surasak Phuphanich, MD, FAAN, Phone: 310-423-3277

Stanford Cancer Center, Stanford, California 94305-5824, United States; Recruiting
Clinical Trials Office - Stanford Cancer Center, Phone: 650-498-7061, Email: cctoffice@stanford.edu

Yale Cancer Center, New Haven, Connecticut 06520-8028, United States; Recruiting
Clinical Trials Office - Yale Cancer Center, Phone: 203-785-5702

Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States; Recruiting
Clinical Trials Office - Robert H. Lurie Comprehensive Cancer, Phone: 312-695-1301, Email: cancer@northwestern.edu

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, Phone: 212-305-8615

Huntsman Cancer Institute at University of Utah, Salt Lake City, Utah 84112, United States; Recruiting
Clinical Trials Office - Huntsman Cancer Institute at Universi, Phone: 801-581-4477, Email: clinical.trials@hci.utah.edu

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109-1024, United States; Recruiting
Clinical Trials Office - Fred Hutchinson Cancer Research Cente, Phone: 800-804-8824

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: December 2008
Last updated: February 6, 2009