Carboplatin Plus Irinotecan in Treating Patients With Glioblastoma Multiforme

Sponsor

NYU Langone Health (Other)

Overall Status

Completed

CT.gov ID

NCT00010036

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: carboplatin Drug: irinotecan hydrochloride Radiation: radiation therapy	Phase 2

Detailed 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)

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I/II Trial of CPT-11 With Carboplatin in Patients With Glioblastoma Multiforme Prior to Radiation Therapy

Study Start Date :

May 1, 1999

Actual Primary Completion Date :

Oct 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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