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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase 2 Study of O-Benzylguanine (O-BG) and Temozolomide in Patients With Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment With Radiation Therapy and Temozolomide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00436436
• Other study ID #: CDR0000529875
• Secondary ID: NCI-07-C-0052AOI
• Status: Completed
• Phase: Phase 2
• First received: February 15, 2007
• Last updated: September 22, 2016
• Start date: December 2006
• Est. completion date: May 2010

Study information

• Verified date: September 2016
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

• WBC = 3,000/mm³

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 10 g/dL (transfusion allowed)

• 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 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 CT scan or 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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• O6-benzylguanine

• temozolomide

Locations

Country	Name	City	State
United States	NCI - Neuro-Oncology Branch	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed best objective tumor response rate (complete or partial response) in patients with methylguanine methyltransferase (MGMT)-positive tumors as assessed by immunohistochemistry (IHC)			No
Secondary	Objective tumor response rate in patients with MGMT-negative tumors as assessed by IHC			No
Secondary	Toxicity as assessed by CTCAE v 3			Yes
Secondary	Best overall response			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No