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A Dose Finding and Safety/Efficacy Trial of CPT-11 (Irinotecan) in Patients With Recurrent Malignant Gliomas

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

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Trial Information

A Dose Finding and Safety/Efficacy Trial of CPT-11 (Irinotecan) in Patients With Recurrent Malignant Gliomas

OBJECTIVES: I. Determine the maximum tolerated dose of intravenous irinotecan when
administered weekly for 4 weeks in patients with recurrent malignant gliomas. II. Describe
the pharmacokinetics of this route of administration, measuring both irinotecan and the
active metabolite SN-38, and determine the effects of hepatic enzyme inducing drugs, such as
anticonvulsants, on the pharmacokinetics in these patients. III. Determine preliminary
response data and activity of irinotecan in this patient population. IV. Correlate response
with topoisomerase I levels in brain tumor tissue from patients undergoing treatment.

OUTLINE: Patients are stratified based on their use/kind of anticonvulsant drugs. This
stratification yields two arms for this study. Arm I consists of patients who use
anticonvulsant drugs that induce hepatic metabolic enzymes. Arm II consists of patients who
use anticonvulsant drugs that cause modest to no induction of hepatic metabolic enzymes or
no anticonvulsant drug. Three patients in each arm receive irinotecan by 90-minute IV
infusions every week for 4 weeks, followed by a 2 week rest period. The dose is escalated
for the next cohort of 3 patients in the absence of unacceptable dose limiting toxicity. The
6 week course is repeated until unacceptable toxicity or disease progression. Once the
maximum tolerated dose has been established for each arm, additional patients are treated at
that dose level. Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 3 patients will be accrued into the phase I portion of the
study and a total of 18-35 patients will be accrued into each arm of the phase II portion of
the study.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma that is progressive or
recurrent following radiation therapy or chemotherapy Anaplastic astrocytoma Glioblastoma
multiforme Low grade glioma that has progressed to biopsy proven high grade glioma is
eligible if the progression occurred after radiotherapy with or without chemotherapy
Measurable progression or recurrence by serial MR or CT imaging

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: Greater than 2 months Hematopoietic: Absolute neutrophil count 1,500/mm3
Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL
Transaminases no greater than 4 times upper limit of normal Renal: Creatinine no greater
than 1.7 mg/dL Cardiovascular: No uncontrolled hypertension No angina pectoris No evidence
of uncontrolled cardiac dysrhythmia Other: No serious infection or other medical illness
No other prior or concurrent malignancy within 5 years except curatively treated basal or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast Not
pregnant or nursing Adequate contraception required of all fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
topoisomerase 1 inhibitor (topotecan, irinotecan, 9- aminocamptothecin) No more that 1
prior chemotherapy regimen At least 6 weeks since nitrosourea and recovered At least 3
weeks since any other chemotherapy and recovered Endocrine therapy: Not specified
Radiotherapy: At least 3 months since completion of most recent course of radiotherapy and
recovered Surgery: Not specified Other: No concurrent investigational agents At least 14
days since prior valproic acid No concurrent valproic acid

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Tracy Batchelor, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Massachusetts General Hospital


United States: Federal Government

Study ID:




Start Date:

July 1998

Completion Date:

April 2004

Related Keywords:

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



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