Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00006025

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

82.8

Actual Duration (Months)

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 I/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: irinotecan hydrochloride Drug: temozolomide	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan when administered with temozolomide in patients with recurrent malignant glioma.
Determine the safety profile of this regimen in this patient population.
Determine the efficacy of this treatment regimen as measured by 6-month progression-free survival and objective tumor response in these patients.
Characterize the pharmacokinetics of this treatment regimen in these patients.
Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, phenobarbital, carbamazepine, or primidone) (yes vs no).

In phase I of the study, patients receive oral temozolomide on days 1-5 and irinotecan IV over 90 minutes on days 1 and 14. Treatment continues every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients concurrently on EIAEDs undergo dose escalation of irinotecan. Cohorts of 3 to 6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

In phase II of the study, patients receive the same treatment as in phase I at the MTD.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months until progression, and then every 4 months for survival.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I within 10 months and 48 patients will be accrued for phase II within 6-8 months.

Study Design

Study Type:

Interventional

Allocation:

N/A

Intervention Model:

Single Group Assignment

Primary Purpose:

Treatment

Official Title:

Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma

Actual Study Start Date :

Jan 5, 2001

Actual Primary Completion Date :

Jan 10, 2005

Actual Study Completion Date :

Dec 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed supratentorial malignant primary glioma of one of the following subtypes:
Glioblastoma multiforme
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Mixed malignant glioma
Original histology of low-grade glioma allowed if subsequent histological confirmation of malignant glioma
Measurable recurrent or residual primary disease by MRI
Lesions with clearly defined margins
Evidence of tumor recurrence or progression by MRI or CT scan
Confirmation of true progressive disease by PET or thallium scan, magnetic resonance spectroscopy, or surgical documentation after prior interstitial brachytherapy or stereotactic radiosurgery
No more than 3 relapses after prior chemotherapy/cytotoxic therapy (including polifeprosan 20 with carmustine implant) for phase I and no more than 2 relapses for phase II

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL

Hepatic:

Bilirubin no greater than 1.5 mg/dL
SGOT no greater than 2 times upper limit of normal

Renal:

Creatinine no greater than 1.5 mg/dL

Cardiovascular:

No uncontrolled hypertension, unstable angina, or symptomatic congestive heart failure
No myocardial infarction within the past 6 months
No serious uncontrolled cardiac arrhythmia

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No mental incapacitation
HIV negative
No AIDS-related disease
No significant ongoing alcoholism or substance abuse
No severe nonmalignant systemic disease
No active infection
No other severe disease that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior interferon or thalidomide and recovered
No concurrent anticancer immunotherapy
No concurrent sargramostim (GM-CSF)
No concurrent prophylactic filgrastim (G-CSF) during first course of study therapy

Chemotherapy:

See Disease Characteristics
Recovered from prior chemotherapy
At least 2 weeks since prior vincristine
At least 3 weeks since prior procarbazine
At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosourea)
Prior radiosensitizers allowed
No prior temozolomide or irinotecan
No other concurrent anticancer chemotherapy

Endocrine therapy:

At least 1 week since prior tamoxifen and recovered
No concurrent anticancer hormonal therapy
Phase II:
Non-increasing dose of corticosteroids allowed

Radiotherapy:

See Disease Characteristics
At least 4 weeks since prior radiotherapy and recovered
No concurrent anticancer radiotherapy

Surgery:

See Disease Characteristics
At least 1-3 weeks since prior surgical resection and recovered

Other:

At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) and recovered
Concurrent enzyme-inducing anti-epileptic drugs with or without steroids allowed
No concurrent valproic acid as a single agent
No concurrent medication that would preclude study (e.g., nonsteroidal immunosuppressive agents)
No other concurrent investigational drugs
No concurrent participation in other clinical study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
4	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
6	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
7	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
8	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-6220
9	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792