Bendamustine Hydrochloride in Treating Patients With Recurrent or Progressive Anaplastic Glioma

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00823797
• Other study ID #: 6803
• Secondary ID: NCI-2010-0071468
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 15, 2009
• Last updated: July 28, 2016
• Start date: October 2008
• Est. completion date: December 2019

Study information

• Verified date: July 2016
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well bendamustine hydrochloride works in treating patients with anaplastic glioma or glioblastoma that has come back (recurrent) or growing, spreading or getting worse (progressive). Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Description:

PRIMARY OBJECTIVES:

I. The primary endpoint for this study is the 6-month progression-free survival-i.e., the proportion of patients who remain alive and free of any tumor progression at 6 months.

SECONDARY OBJECTIVES:

I. To determine the safety of single agent bendamustine (Treanda) (bendamustine hydrochloride) the treatment of malignant gliomas.

II. To determine the efficacy of bendamustine (Treanda) as a single agent as assessed by progression-free survival (PFS) at 6 months.

III. To assess quality of life using the Functional Assessment of Cancer Therapy-Brain (FACT-BR).

OUTLINE:

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

After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: December 2019
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients must have had prior pathologic confirmation of tumor histology, anaplastic glioma (AG) or glioblastoma (GBM) and have supratentorial gliomas

• Patients must have shown unequivocal evidence for tumor recurrence or progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan with contrast

• The recurrence to be treated needs to be the 1st or 2nd recurrence of the AG or GBM

• If a patient has had surgery prior to enrolling on study, an enhanced MRI or CT scan should be done within 96 hours prior to surgery or at least 4-6 weeks after surgery

• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

• They are > 2 weeks from surgery

• They have recovered from the effects of surgery

• Evaluable or measurable disease following resection of recurrent tumor is mandated for eligibility into the study

• To best assess the extent of residual disease post-operatively, an enhanced CT/MRI should be done no later than 96 hours after surgery or it will need to be done 4-6 weeks post-operatively; if the 96 hour scan is more than 2 weeks from registration, the scan needs to be repeated

• A baseline scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for at least 5 days otherwise a new baseline MR/CT is required; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement

• Patients must have failed prior external beam radiation therapy; a positron emission tomography (PET) or thallium single photon emission computed tomography (SPECT), MR spectroscopy and MR perfusion, or surgical documentation may be done at the discretion of the treating physician if there is a question of radiation changes/necrosis versus progressive disease

• Stereotactic radiosurgery (SRS):

• Patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease

• At least 12 weeks between completion of SRS and initiation of bendamustine

• Interstitial brachytherapy: patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease

• Patients must have had at least one prior chemotherapy regimen that included temozolomide and no more than one prior salvage chemotherapy

• Patients must have recovered from the toxic effects of prior therapy: 4 weeks from prior cytotoxic therapy and/or at least 2 weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count), 4 weeks for experimental biologic agents (epidermal growth factor receptor [EGFR] inhibitors, etc) and 7 weeks from Gliadel implantation

• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information

• Patients must have a life expectancy > 11 weeks

• Patients must have a Karnofsky performance status of > 60

• White blood cells (WBC) >= 3,000/ul

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 80,000/mm^3

• Hemoglobin >= 9 mg/dl (NOTE: eligibility level for hemoglobin may be reached by transfusion)

• Absolute lymphocyte count >= 200/mm^3

• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) < 3 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Serum creatinine < 1.5 mg/dL

• Calculated creatinine, glomerular filtration rate (GFR) >= 30 cc/minute

Exclusion Criteria:

• Patients must not have any 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

• Known human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study

• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible

• Patients must not be pregnant or breast feeding and must practice adequate contraception

• Patients can only be on non-enzyme inducing anti-convulsants; if they are on an enzyme inducing anti-convulsant, they may be converted to a non-enzyme inducing anticonvulsants

• Patients cannot be taking any cytochrome P450, cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) pathway inhibiting or inducing agents (except proton pump inhibitors which are allowed) including cimetidine, antidepressants, antibiotics and all others

• Known sensitivity to bendamustine

• Known sensitivity to mannitol

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Anaplastic Astrocytoma
• Adult Anaplastic Oligodendroglioma
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Astrocytoma
• Brain Neoplasms
• Glioblastoma
• Gliosarcoma
• Oligodendroglioma
• Recurrent Adult Brain Neoplasm

Intervention

Drug:
• Bendamustine Hydrochloride
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI), National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	Defined as the proportion of patients who remain alive and free of any disease progression at 6 months. PFS over time will be estimated using the Kaplan-Meier method with standard errors estimated using Greenwood's formula.	At 6 months	No
Secondary	Best overall response		Up to 12 months	No
Secondary	PFS	Defined as the time from date of initial therapy to first objective documentation of tumor progression or death. PFS over time will be estimated using the Kaplan-Meier method with standard errors estimated using Greenwood's formula.	At 6 months	No
Secondary	Quality of life, assessed by the FACT-BR total score	FACT-BR total score trajectories will be examined for each patient, and for groups defined by length of follow-up. Quality of life data will be used to quantify the impact of adverse events on patient quality of life.	Up to 3 years	No
Secondary	Toxic death	Defined as death that is possibly, probably, or definitely attributed to bendamustine hydrochloride.	Up to 30 days after completion of study treatment	Yes
Secondary	Toxicity that results in significant reduction in or cessation of bendamustine hydrochloride treatment	All reported adverse events will be coded using the Cancer Therapy Evaluation Program Common Toxicity Criteria. The number and percent of subjects reporting adverse events (all, severe or worse, serious and related) will be quantified.	Up to 30 days after completion of study treatment	Yes