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Irinotecan in Treating Patients With Progressive or Recurrent Malignant Glioma

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
irinotecan hydrochloride
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent adult brain tumor, adult brain stem glioma, adult oligodendroglioma, adult mixed glioma, adult diffuse astrocytoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jonsson Comprehensive Cancer Center, UCLA
  • UCSF Cancer Center and Cancer Research Institute
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • University of Pittsburgh Cancer Institute
  • Children's Hospital of Pittsburgh
  • Simmons Cancer Center - Dallas
  • University of Texas - MD Anderson Cancer Center
  • University of Texas Health Science Center at San Antonio
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
June 25, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003616
Brief Title
Irinotecan in Treating Patients With Progressive or Recurrent Malignant Glioma
Official Title
Phase I/II Trial of Irinotecan (CPT-11) in Patients With Recurrent Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 22, 1998 (Actual)
Primary Completion Date
May 17, 2002 (Actual)
Study Completion Date
December 20, 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of irinotecan in treating patients who have progressive or recurrent malignant glioma.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
recurrent adult brain tumor, adult brain stem glioma, adult oligodendroglioma, adult mixed glioma, adult diffuse astrocytoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Prados, MD
Organizational Affiliation
UCSF Medical Center at Parnassus
Official's Role
Study Chair
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-3489
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16533878
Citation
Prados MD, Lamborn K, Yung WK, Jaeckle K, Robins HI, Mehta M, Fine HA, Wen PY, Cloughesy T, Chang S, Nicholas MK, Schiff D, Greenberg H, Junck L, Fink K, Hess K, Kuhn J; North American Brain Tumor Consortium. A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol. 2006 Apr;8(2):189-93. doi: 10.1215/15228517-2005-010. Epub 2006 Mar 13.
Results Reference
result
PubMed Identifier
14769140
Citation
Prados MD, Yung WK, Jaeckle KA, Robins HI, Mehta MP, Fine HA, Wen PY, Cloughesy TF, Chang SM, Nicholas MK, Schiff D, Greenberg HS, Junck L, Fink KL, Hess KR, Kuhn J; North American Brain Tumor Consortium study. Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol. 2004 Jan;6(1):44-54. doi: 10.1215/S1152851703000292.
Results Reference
result

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Irinotecan in Treating Patients With Progressive or Recurrent Malignant Glioma

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