Carboplatin Plus Irinotecan in Treating Patients With Glioblastoma Multiforme

NYU Langone Health

Status and phase: Completed; Phase 2

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: carboplatin; Drug: irinotecan hydrochloride; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00010036

NCI-G00-1909

CDR0000068435

P-UPJOHN-986475197

NYU-9902

P30CA016087 (U.S. NIH Grant/Contract)

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 II trial to study the effectiveness of combining carboplatin with irinotecan in treating patients who have glioblastoma multiforme.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of carboplatin and irinotecan in patients with glioblastoma multiforme. (Phase I closed to accrual as of 6/24/02)
• Determine the toxic effects of this regimen in these patients.
• Determine the objective response in patients treated with the established MTD of this regimen.
• Determine time to tumor progression and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study. Patients in the phase II portion of the study are stratified according to age (under 60 vs 60 and over), ECOG performance status (0-1 vs 2), and extent of resection (total vs subtotal). (Phase I closed to accrual as of 6/24/02)

Within 4 weeks of surgery, patients receive carboplatin IV over 30 minutes followed by irinotecan IV over 90 minutes on day 1. Treatment repeats every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive carboplatin and irinotecan at the recommended phase II dose. (Phase I closed to accrual as of 6/24/02)

After chemotherapy, all patients undergo radiotherapy.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 24-107 patients (3-54 for phase I and 21-53 for phase II) will be accrued for this study. (Phase I closed to accrual as of 6/24/02)

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme
• Measurable disease
• No CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 70-100%

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver involvement)
• No known Gilbert's syndrome

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy

Other:

• HIV negative
• No active or uncontrolled infection
• No psychiatric disorder that would preclude study
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No uncontrolled diabetes mellitus (i.e., random blood sugar of 200 mg or more)
• No other severe disease that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy or biologic therapy
• No concurrent sargramostim (GM-CSF)
• No concurrent filgrastim (G-CSF) with course 1
• No concurrent immunotherapy

Chemotherapy:

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Must have maintained a stable or decreasing dose of corticosteroids for 2 weeks prior to study
• Concurrent corticosteroids for cerebral edema allowed
• No concurrent anticancer hormonal therapy

Radiotherapy:

• No prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since prior surgery

Other:

• No other concurrent investigational agent or participation on any other clinical study
• No concurrent immunosuppressive drugs
• No concurrent phenobarbital or valproic acid
• No concurrent anticonvulsants except carbamazepine or gabapentin
• No concurrent prochlorperazine on day of irinotecan treatment