Karenitecin in Treating Patients With Recurrent Malignant Glioma

Phase I Evaluation Of The Safety Of Karenitecin In The Treatment Of Recurrent Malignant Gliomas

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of karenitecin in treating patients who have recurrent malignant glioma.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: karenitecin

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of karenitecin in patients with recurrent malignant glioma who are receiving or not receiving anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.
• Determine the pharmacokinetics of this drug in these patients.
• Assess the preliminary evidence of therapeutic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to use of anticonvulsants known to be metabolized by the P450 hepatic enzyme complex (yes vs no).

Patients receive karenitecin IV over 60 minutes on days 1-5. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of karenitecin according to the continual reassessment method until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose associated with a dose-limiting toxicity rate of 33%.

Patients are followed every 2 months.

PROJECTED ACCRUAL: Approximately 3-24 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1030
      • Comprehensive Cancer Center at Wake Forest University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme

• Progressive or recurrent disease previously treated with radiotherapy with or without chemotherapy

  • Prior low-grade disease that progressed to high-grade after therapy allowed
• Measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 8.5 g/dL

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

Other:

• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No serious concurrent infection
• No other medical illness that would preclude study
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No more than 1 prior chemotherapy regimen

Endocrine therapy:

• Must be on stable dose of steroids for at least 5 days

Radiotherapy:

• See Disease Characteristics
• At least 3 months since prior radiotherapy and recovered
• No more than 1 prior course of radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational agents
• At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2002

Study Registration Dates

• First Submitted: April 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 24, 2008
• Last Update Submitted That Met QC Criteria: July 23, 2008
• Last Verified: February 1, 2005

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: CDR0000068552; NABTT-2006; JHOC-NABTT-2006