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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

O6-benzylguanine

temozolomide

conventional surgery

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Duke Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00006474

First Posted

November 6, 2000

Last Updated

June 19, 2013

Sponsor

Duke University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00006474

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

March 2001 (undefined)

Primary Completion Date

August 2004 (Actual)

Study Completion Date

August 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Duke University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain and Central Nervous System Tumors

Keywords

recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

O6-benzylguanine

Intervention Type

Drug

Intervention Name(s)

temozolomide

Intervention Type

Procedure

Intervention Name(s)

conventional surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Henry S. Friedman, MD

Organizational Affiliation

Duke Cancer Institute

Official's Role

Study Chair

Facility Information:

Facility Name

Duke Comprehensive Cancer Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19289491

Citation

Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, Gururangan S, Friedman AH, Bigner DD, Sampson JH, McLendon RE, Herndon JE Jr, Walker A, Friedman HS. Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma. Neuro Oncol. 2009 Oct;11(5):556-61. doi: 10.1215/15228517-2009-007. Epub 2009 Mar 16.

Results Reference

result

PubMed Identifier

16192602

Citation

Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE 2nd, Bigner DD, Friedman HS. Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1;23(28):7178-87. doi: 10.1200/JCO.2005.06.502.

Results Reference

result

Brain and Central Nervous System Tumors

About this trial

Eligibility Criteria

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial