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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Recurrent Adult Brain Tumor

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Trial Information

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


PRIMARY OBJECTIVES:

I. The primary endpoint for this study is the 6-month progression-free survival (PFS) (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 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 for 30 days and then every 3
months thereafter.


Inclusion Criteria:



- All patients must have had prior pathologic confirmation of tumor histology,
anaplastic glioma (AG) [anaplastic astrocytomas (AA), anaplastic oligodendrogliomas
(AO) or anaplastic oligoastrocytomas (AOA)] 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

- 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 10 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 glutamic pyruvic 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 because of possible
pharmacokinetic interactions; HIV testing is not required for study participation

- 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 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

PFS

Outcome Description:

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.

Outcome Time Frame:

At 6 months

Safety Issue:

No

Principal Investigator

Marc Chamberlain

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

6803

NCT ID:

NCT00823797

Start Date:

October 2008

Completion Date:

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Recurrent Adult Brain Tumor
  • Astrocytoma
  • Brain Neoplasms
  • Glioma
  • Oligodendroglioma

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Northwestern UniversityChicago, Illinois  60611
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112