O6-Benzylguanine and Carmustine Implants in Treating Patients With Recurrent Malignant Glioma

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

O6-benzylguanine

polifeprosan 20 with carmustine implant

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 brain stem glioma, adult ependymoma, adult glioblastoma, adult oligodendroglioma, adult anaplastic astrocytoma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma determined from prior stereotactic biopsy or cytoreductive surgery for removal of a supratentorial brain tumor Unilateral supratentorial tumor, measuring at least 1 cm, as determined by CT scan or MRI No more than 1 focus of tumor and no tumor crossing the midline Surgical treatment indicated at baseline evaluation Received prior definitive (greater than 5,000 cGy) external beam radiotherapy more than 3 months ago Evidence of progression At time of tumor resection and Gliadel wafers implantation: Intraoperative pathological diagnosis on frozen section or squash preparation of malignant glioma OR Glioblastoma multiforme or anaplastic astrocytoma on permanent sections from a prior surgery and an intraoperative pathological diagnosis on frozen section or squash preparation of tumor, glioma, or malignant glioma (not necrosis) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 60 days Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.7 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 1 year after surgery No other concurrent significant life threatening disease No known hypersensitivity to nitrosoureas No other malignancy in past five years except curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered No other concurrent chemotherapy during first 56 days of study Endocrine therapy: No concurrent dexamethasone as an antiemetic Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

Sites / Locations

University of Alabama Comprehensive Cancer Center
H. Lee Moffitt Cancer Center and Research Institute
Emory University Hospital - Atlanta
Johns Hopkins Oncology Center
Massachusetts General Hospital Cancer Center
Henry Ford Hospital
Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
University of Pennsylvania Cancer Center
University of Texas Health Science Center at San Antonio

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00004892

First Posted

March 7, 2000

Last Updated

February 6, 2009

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00004892

Brief Title

O6-Benzylguanine and Carmustine Implants in Treating Patients With Recurrent Malignant Glioma

Official Title

Phase I GLIADEL and Continuous Infusion of Intravenous O6-Benzylguanine Trial in Patients With Recurrent Malignant Glioma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2007

Overall Recruitment Status

Completed

Study Start Date

April 2000 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

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 and giving drugs in different ways may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of O6-benzylguanine and implanted carmustine wafers in treating patients who have recurrent malignant glioma.

Detailed Description

OBJECTIVES: I. Determine the dose of O6-benzylguanine that completely suppresses AGT levels in patients with recurrent malignant glioma. II. Evaluate the safety and tolerance of increasing duration for up to 2 weeks of continuously infused O6-benzylguanine at a dose that will completely suppress tumor AGT activity combined with intracranially implanted polifeprosan 20 with carmustine implants (Gliadel wafers) in this patient population. OUTLINE: This is a dose escalation study of O6-benzylguanine (O6-BG). Patients in the first cohort receive O6-BG IV over 1 hour followed by continuous infusion of O6-BG for 2 days prior to surgery. Patients undergo surgical resection and receive up to 8 polifeprosan 20 with carmustine implants (Gliadel wafers) in the resected tumor cavity. Cohorts of 14 patients receive escalating doses of O6-BG until 11 out of 14 patients in a cohort have complete suppression of AGT levels. Once the dose of O6-BG that completely suppresses AGT has been established, subsequent patients receive O6-BG IV beginning at least 1 hour prior to surgery followed by the established continuous infusion dose beginning on the day of surgery. The infusion continues for up to 14 days postoperatively. Cohorts of 6-12 patients receive lengthened durations of continuous infusion O6-BG until the maximum tolerated dose (MTD) is determined or the length of the infusion reaches 14 days. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of 12 patients experience dose limiting toxicities. Patients are followed at 3, 6, 9, and 12 months, and then until death. PROJECTED ACCRUAL: A minimum of 38 patients will be accrued for this study over 9.5 months.

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 brain stem glioma, adult ependymoma, adult glioblastoma, adult oligodendroglioma, adult anaplastic astrocytoma, adult mixed glioma, 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)

polifeprosan 20 with carmustine implant

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: Histologically confirmed malignant glioma determined from prior stereotactic biopsy or cytoreductive surgery for removal of a supratentorial brain tumor Unilateral supratentorial tumor, measuring at least 1 cm, as determined by CT scan or MRI No more than 1 focus of tumor and no tumor crossing the midline Surgical treatment indicated at baseline evaluation Received prior definitive (greater than 5,000 cGy) external beam radiotherapy more than 3 months ago Evidence of progression At time of tumor resection and Gliadel wafers implantation: Intraoperative pathological diagnosis on frozen section or squash preparation of malignant glioma OR Glioblastoma multiforme or anaplastic astrocytoma on permanent sections from a prior surgery and an intraoperative pathological diagnosis on frozen section or squash preparation of tumor, glioma, or malignant glioma (not necrosis) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 60 days Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.7 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 1 year after surgery No other concurrent significant life threatening disease No known hypersensitivity to nitrosoureas No other malignancy in past five years except curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered No other concurrent chemotherapy during first 56 days of study Endocrine therapy: No concurrent dexamethasone as an antiemetic Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jon Weingart, MD

Organizational Affiliation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Official's Role

Study Chair

Facility Information:

Facility Name

University of Alabama Comprehensive Cancer Center

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

H. Lee Moffitt Cancer Center and Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Emory University Hospital - Atlanta

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Johns Hopkins Oncology Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

Massachusetts General Hospital Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Henry Ford Hospital

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157-1082

Country

United States

Facility Name

University of Pennsylvania Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78284-7811

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17264335

Citation

Weingart J, Grossman SA, Carson KA, Fisher JD, Delaney SM, Rosenblum ML, Olivi A, Judy K, Tatter SB, Dolan ME. Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous O6-benzylguanine in adults with recurrent malignant glioma: new approaches to brain tumor therapy CNS consortium trial. J Clin Oncol. 2007 Feb 1;25(4):399-404. doi: 10.1200/JCO.2006.06.6290.

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