Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00006474
First received: November 6, 2000
Last updated: June 19, 2013
Last verified: February 2013
  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

Resource links provided by NLM:


Further study details as provided by Duke University:

Study Start Date: March 2001
Study Completion Date: August 2004
Primary Completion Date: August 2004 (Final data collection date for primary outcome measure)
Detailed Description:

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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006474

Locations
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
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: 1388, DUMC-1388-02-8R2, DUMC-1388-00-8, NCI-490, DUMC-1388-01-8R1, CDR0000068301
Study First Received: November 6, 2000
Last Updated: June 19, 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 July 29, 2014