Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

NCT ID: NCT00006025

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-05
• Study Completion Date: 2007-12-01

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.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT

Interventions

irinotecan hydrochloride

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wai-Kwan A. Yung, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

Loghin ME, Prados MD, Wen P, Junck L, Lieberman F, Fine H, Fink KL, Metha M, Kuhn J, Lamborn K, Chang SM, Cloughesy T, DeAngelis LM, Robins IH, Aldape KD, Yung WK. Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in patients receiving enzyme-inducing antiepileptic drugs: a north american brain tumor consortium study. Clin Cancer Res. 2007 Dec 1;13(23):7133-8. doi: 10.1158/1078-0432.CCR-07-0874.

Reference Type: RESULT

PMID: 18056194 (View on PubMed)

Other Identifiers

CDR0000068037

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCLA-0006095

Identifier Type: -

Identifier Source: secondary_id

NCI-2012-02353

Identifier Type: REGISTRY

Identifier Source: secondary_id

NABTC-9907

Identifier Type: -

Identifier Source: org_study_id