O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy

NCT ID: NCT00436436

Last Updated: 2017-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-13
• Study Completion Date: 2010-04-14

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as O(6)-benzylguanine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving O(6)-benzylguanine together with temozolomide works in treating patients with glioblastoma multiforme that did not respond to previous temozolomide and radiation therapy.

Detailed Description

OBJECTIVES:

• Determine the antitumor activity of O6-benzylguanine and temozolomide in patients with temozolomide-resistant methylguanine methyltransferase-positive or -negative glioblastoma multiforme previously treated with radiotherapy.
• Determine, preliminarily, the toxicity of this regimen in these patients.

OUTLINE: Patients receive O6-benzylguanine intravenous (IV) over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 6 months.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

O6-benzylguanine & Temozolomide in Glioblastoma

Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

O6-benzylguanine

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

Interventions

O6-benzylguanine

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

Other Intervention Names

06-BG; Temodar

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme (GBM), including the following:

• Small or large cell GBM
• Gliosarcoma
• Temozolomide-resistant disease, as defined by the following:

• Unequivocal evidence of tumor progression after receiving adjuvant temozolomide therapy for 5 consecutive days every 28 days for ≥ 2 courses
• Must have failed prior radiotherapy

• Progression must be documented by MRI (while on a stable steroid dose for ≥ 5 days) ≥ 12 weeks after completion of radiotherapy
• Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded microscope slides available from diagnosis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy > 8 weeks
• White blood cell (WBC) ≥ 3,000/mm(³)
• Absolute neutrophil count ≥ 1,500/mm(³)
• Platelet count ≥ 100,000/mm(³)
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Aspartate aminotransaminase (AST) < 2 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• No significant medical illness that, in the opinion of the investigator, would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant active cardiac, hepatic, renal, or psychiatric disease
• No other known active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active infection requiring intravenous (IV) antibiotics
• No disease that would obscure toxicity or alter drug metabolism

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior temozolomide
• Prior resection of recurrent or progressive tumor allowed if all the following criteria are met:

• Recovered from prior surgery
• Residual disease after resection of recurrent tumor by computed tomography (CT) scan or magnetic resonance imaging (MRI) (while on a stable steroid dose for ≥ 5 days) ≤ 96 hours OR ≥ 4 weeks after surgery
• At least 12 weeks since prior radiotherapy
• No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel wafers] or nitrosoureas)
• No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Mark Gilbert, M.D.

Branch Chief, Neuro-Oncology Branch

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Howard A Fine, M.D.

Role: PRINCIPAL_INVESTIGATOR

NCI - Neuro-Oncology Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

NCI - Neuro-Oncology Branch

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

NCI-07-C-0052

Identifier Type: -

Identifier Source: secondary_id

AOI-NCI-07-C-0052

Identifier Type: -

Identifier Source: secondary_id

CDR0000529875

Identifier Type: OTHER

Identifier Source: secondary_id

070052

Identifier Type: -

Identifier Source: org_study_id