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Phase I/II Trial of Irinotecan (CPT-11) 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 Irinotecan (CPT-11) in Patients With Recurrent Malignant Glioma

OBJECTIVES: I. Determine the maximum tolerated dose and the dose limiting toxicities of
irinotecan in patients with progressive or recurrent malignant glioma. II. Define the safety
profile of every 3 week dosing of irinotecan in these patients. III. Characterize the
pharmacokinetic profile of this regimen in these patients. IV. Assess evidence of antitumor
activity in these patients. V. Determine the efficacy of irinotecan in these patients as
measured by 6 month progression-free survival and objective tumor response. VI. Evaluate
further the safety profile of irinotecan in these patients during phase II study.

OUTLINE: This is a dose escalation study. Patients are stratified according to concurrent
enzyme-inducing antiepileptic drugs (EIAEDs)(yes vs no). Group A (without EIAEDs): Patients
receive irinotecan IV over 90 minutes on day 1, followed by up to 3 weeks of rest. Group B
(with EIAEDs): Patients receive the same treatment but dose escalation is performed in
cohorts of 3 patients. The maximum tolerated dose (MTD) is defined as the dose below that at
which 2 of 6 patients experience dose limiting toxicities. The Phase I MTD is the starting
dose recommended for use in the Phase II portion of the study. Treatment continues every 3
weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
for 1 year, then every 6 months until disease progression. Patients are then followed every
4 months for survival.

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

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven progressive or recurrent primary malignant
glioma Phase I (excluding group A patients): No more than 2 prior chemotherapy regimens,
including 1 prior adjuvant therapy and 1 prior regimen for recurrent or progressive tumor,
or 2 prior regimens for progressive tumor Phase II and/or group A patients: No more than 1
prior chemotherapy regimen, either as adjuvant or for recurrent disease Measurable disease
by MRI or CT scan

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: Not specified Hematopoietic: Neutrophil count at least 1,500/mm3 Platelet
count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater
than 3 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL
Cardiovascular: No uncontrolled hypertension No unstable angina No symptomatic congestive
heart failure No myocardial infarction within 6 months No serious uncontrolled cardiac
arrhythmia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must
use effective contraception No severe nonmalignant systemic disease or active infection No
concurrent alcoholism or drug abuse No psychosis HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent
sargramostim (GM-CSF) Chemotherapy: See Disease Characteristics At least 4 weeks since
prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or suramin) No prior irinotecan,
topotecan, or other topotecan 1 inhibitors No other concurrent chemotherapy Endocrine
therapy: Stable or decreasing dosage of corticosteroids within 72 hours of study entry
(phase II only) No other concurrent immunosuppressive agents No concurrent hormonal
therapy Radiotherapy: At least 4 weeks since prior radiotherapy Patients with prior
interstitial brachytherapy or stereotactic radiosurgery must have confirmation of
progressive disease No concurrent radiotherapy Surgery: At least 3 weeks since prior
resection Other: Acute toxic effects (excluding neurotoxicity or alopecia) of any prior
therapy must be resolved No concurrent valproic acid as a single agent Concurrent
enzyme-inducing antiepileptic drugs (EIAED) with or without steroids are allowed No
concurrent investigational drugs

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael Prados, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UCSF Medical Center at Parnassus


United States: Federal Government

Study ID:




Start Date:

September 1998

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult brain stem glioma
  • adult oligodendroglioma
  • adult mixed glioma
  • adult diffuse astrocytoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781
Simmons Cancer Center - Dallas Dallas, Texas  75235-9154
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
UCSF Cancer Center and Cancer Research Institute San Francisco, California  94115-0128
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213