Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	NABTC-9907 UCLA-0006095, NCT00006025

Objectives

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

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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.

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.

Loghin ME, Prados MD, Wen P, et al.: 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 13 (23): 7133-8, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North American Brain Tumor Consortium

Wai-Kwan Yung, MD, Protocol chair		Ph: 713-794-1285; 800-392-1611

Registry Information
Official Title		Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients with Recurrent Malignant Glioma
Trial Start Date		2000-11-14
Trial Completion Date		2008-05-07
Registered in ClinicalTrials.gov		NCT00006025 1
Date Submitted to PDQ		2000-05-30
Information Last Verified		2004-08-27
NCI Grant/Contract Number		CA62399

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00006025