Carmustine Wafers Plus Irinotecan in Treating Patients With Recurrent Supratentorial High Grade Gliomas

Duke University

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: irinotecan hydrochloride; Drug: carmustine; Procedure: surgical procedure; Drug: polifeprosan 20 with carmustine implant

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003463

DUMC-0901-01-5R3

DUMC-0797-99-5RI

DUMC-0901-02-5R4

DUMC-000901-00-5R2

CDR0000066497 (Other Identifier)

0901

UCLA-9812060

DUMC-796-98-5

DUMC-98065

DUMC-0901-02-5R2

DUMC-000901-01-5R3

NCI-G98-1464

Details and patient eligibility

About

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 carmustine wafers plus irinotecan in treating patients with recurrent supratentorial high grade gliomas.

Full description

OBJECTIVES:

• Define the maximum tolerated dose of irinotecan given in combination with Gliadel wafers (carmustine) in patients with recurrent glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.
• Define the toxicity of irinotecan given in combination with Gliadel wafers in these patients.

OUTLINE: This is a dose escalation study.

All patients undergo surgical resection. At the time of surgery, up to eight Gliadel wafers (containing carmustine) are implanted in the resected tumor cavity.

Cohorts of 3 patients each receive escalating doses of irinotecan IV over 90 minutes once weekly within 3 weeks after Gliadel wafer implantation. One course of treatment consists of 4 weeks of irinotecan and 2 weeks of rest. If 1 patient experiences dose limiting toxicity (DLT) at a dose level, an additional 3 patients are entered at that same dose level. If 2 patients experience DLT, the maximum tolerated dose (MTD) has been surpassed and a total of 6 patients are treated at the previous dose level. The MTD is defined as the highest dose in which no more than 1 of 6 patients experiences DLT.

Treatment continues for up to 12 courses in the absence of unacceptable toxicity and disease progression.

Patients are followed for at least 4 months.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued into this study over 9 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent supratentorial glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma
• Must be able to undergo surgical resection
• At least 1 bidimensionally measurable lesion documented on Gd-MRI within 72 hours after surgical implantation of Gliadel wafers
• Not requiring immediate radiotherapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Greater than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 125,000/mm^3
• Hematocrit at least 29%

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT or SGPT less than 2.5 times ULN
• Alkaline phosphatase less than 2 times ULN

Renal:

• BUN less than 1.5 times ULN
• Creatinine less than 1.5 times ULN

Neurological:

• Must be neurologically stable

Other:

• HIV negative

  • No AIDS-related illness

• No nonmalignant systemic disease that would make patient a poor medical risk

• No acute infection requiring intravenous antibiotics

• Not pregnant or nursing

  • Negative pregnancy test 24 hours prior to study

• Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior irinotecan
• At least 6 weeks since chemotherapy unless there is unequivocal evidence of tumor progression after chemotherapy

Endocrine therapy:

• At least 1 week of nonincreasing dose of steroids prior to study

Radiotherapy:

• At least 6 weeks since radiotherapy unless there is unequivocal evidence of tumor progression after radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified