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

Phase 1/Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

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


- 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.

Inclusion Criteria


- 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



- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Not specified


- 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


- Bilirubin no greater than 1.5 mg/dL

- SGOT no greater than 2 times upper limit of normal


- Creatinine no greater than 1.5 mg/dL


- No uncontrolled hypertension, unstable angina, or symptomatic congestive heart

- No myocardial infarction within the past 6 months

- No serious uncontrolled cardiac arrhythmia


- 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


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


- 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


- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- No concurrent anticancer radiotherapy


- See Disease Characteristics

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


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Wai-Kwan A. Yung, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Federal Government

Study ID:




Start Date:

November 2000

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult anaplastic oligodendroglioma
  • adult mixed glioma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
UCSF Comprehensive Cancer Center San Francisco, California  94115
Hillman Cancer Center at University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15236
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182