Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating patients who have newly diagnosed, recurrent, or progressive anaplastic glioma.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: O6-benzylguanine Drug: temozolomide Procedure: conventional surgery |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | Phase I Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Newly Diagnosed (Part 1) or Recurrent/Progressive (Parts 1 and 2) Cerebral Anaplastic Gliomas |
| Study Start Date: | March 2001 |
| Study Completion Date: | August 2004 |
| Primary Completion Date: | August 2004 (Final data collection date for primary outcome measure) |
OBJECTIVES:
- Determine the dose of O6-benzylguanine (O6-BG) effective in producing complete suppression of tumor O6-alkylguanine-DNA alkyltransferase activity in patients with newly diagnosed (closed to accrual 12/19/2000) or recurrent or progressive cerebral anaplastic glioma.
- Determine the maximum tolerated dose of temozolomide administered after O6-BG in these patients.
- Determine the toxicity of this regimen in these patients.
- Determine the anti-tumor response in patients treated with this regimen.
OUTLINE: This is a dose-escalation, multicenter study.
- Part I: Patients receive escalating doses of O6-benzylguanine (O6-BG) IV continuously for 49 hours until the dose that produces the target depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) is determined. Patients undergo a craniotomy after completion of the O6-BG infusion. (closed to accrual 12/19/2000)
- Part II: After determination of the O6-BG dose in Part I, patients with recurrent malignant gliomas receive O6-BG IV continuously for 49 hours beginning on day 1. Patients also receive oral temozolomide on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 20-30 patients (with 14 patients participating in Part II) will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Part I:
- Histologically confirmed, newly diagnosed glioblastoma multiforme or anaplastic astrocytoma (closed to accrual 12/19/2000)
Parts I and II:
Histologically confirmed astrocytic, oligodendroglial, or mixed glial tumor
- Grade III or higher
- Recurrent or progressive after radiotherapy
- Evaluable residual disease by contrast-enhanced MRI or CT scan
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic:
- SGOT no greater than 2.5 times upper limit of normal
- Bilirubin normal
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
- BUN no greater than 25 mg/dL
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 6 weeks since prior biologic therapy and recovered
Chemotherapy:
At least 2 weeks since prior chemotherapy (including but not limited to topotecan) and recovered
Patients in trials with one of the following treatment combinations are allowed to enroll 6 weeks after receiving carmustine (BCNU):
- BCNU on day 1
- BCNU on day 1 and topotecan on days 1, 8, 15, 22, 29, and 36
- BCNU on day 1 and irinotecan on days 1, 8, 15, and 22
Endocrine therapy:
- Patients on corticosteroids must be on a stable dose for at least 2 weeks before study
- At least 6 weeks since other prior endocrine therapy and recovered
Radiotherapy:
- See Disease Characteristics
- At least 6 weeks since prior radiotherapy and recovered
Surgery:
- Not specified
Contacts and Locations| United States, North Carolina | |
| Duke Comprehensive Cancer Center | |
| Durham, North Carolina, United States, 27710 | |
| Study Chair: | Henry S. Friedman, MD | Duke Cancer Institute |
More Information
Additional Information:
Publications:
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00006474 History of Changes |
| Other Study ID Numbers: | CDR0000068301, 1388, DUMC-1388-02-8R2, DUMC-1388-00-8, NCI-490, DUMC-1388-01-8R1 |
| Study First Received: | November 6, 2000 |
| Last Updated: | March 26, 2013 |
| Health Authority: | United States: Federal Government United States: Institutional Review Board |
Keywords provided by Duke University:
|
recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma |
adult mixed glioma adult oligodendroglioma adult giant cell glioblastoma adult gliosarcoma |
Additional relevant MeSH terms:
|
Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site |
Nervous System Diseases Temozolomide O(6)-benzylguanine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013