Clinical trial NCT00010036: Carboplatin Plus Irinotecan in Treating Patients With Glioblastoma Multiforme
Official title: A Phase I/II Trial of CPT-11 With Carboplatin in Patients With Glioblastoma Multiforme Prior to Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-04
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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)

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Michael L. Gruber, MD
role: STUDY_CHAIR
References: