A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma

February 7, 2012 updated by: Keryx / AOI Pharmaceuticals, Inc.
This is an open-label, multicenter, phase II trial, assessing the antitumor activity, and safety of temozolomide in combination with O6-BG in patients with temozolomide-resistant anaplastic glioma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This open-label, multicenter, phase II trial will assess the antitumor activity and safety of temozolomide in combination with O6-BG in patients with temozolomide-resistant anaplastic glioma.

Forty-one to 104 evaluable patients with temozolomide-resistant anaplastic glioma will be enrolled in this study. Total accrual on this study will not exceed 116 patients. The patients will receive daily temozolomide on 5 consecutive days (days 1-5) along with bolus infusions of O6-BG on days 1, 3, and 5 and a continuous infusion of O6-BG beginning immediately after the first bolus infusion and continuing until immediately prior to the last bolus injection. Patients will be evaluated for AEs during the course of therapy. Patients may receive treatment at the same dose level until appearance of significant treatment-related toxicities, disease progression or withdrawal of consent.

Tumor response will be evaluated at the end of cycle 1, cycle 2 and then every two cycles for the duration of therapy, using physical and neurological examinations and diagnostic imaging.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • AOI Pharmaceuticals Investigative Site
    • Florida
      • Orlando, Florida, United States, 32804
        • AOI Pharmaceuticals Investigative Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • AOI Pharmaceuticals Investigative Site
      • Evanston, Illinois, United States, 60201
        • AOI Pharmaceuticals Investigative Site
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • AOI Pharmaceuticals Investigative Site
      • Louisville, Kentucky, United States, 40202
        • AOI Pharmaceuticals Investigative Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 54407
        • AOI Pharmaceuticals Investigative Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • AOI Pharmaceuticals Investigative Site
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • AOI Pharmaceuticals Investigative Site
    • Texas
      • Dallas, Texas, United States, 75246
        • AOI Pharmaceuticals Investigative Site
      • Houston, Texas, United States, 77024
        • AOI Pharmaceuticals Investigative Site
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • AOI Pharmaceuticals Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with histologically documented anaplastic glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or mixed anaplastic oligoastrocytoma).
  2. Temozolomide-resistant defined as patients who have progressed while receiving or within 8 weeks of completing the last dose of temozolomide.
  3. Disease progression >= 12 weeks after the completion of any radiotherapy.
  4. If patient received chemotherapy or an investigational agent as part of their prior therapy, the patient must recover from all toxicities (<= Grade 1) prior to enrollment on this protocol.
  5. Bi-dimensionally measurable disease on contrast-enhanced magnetic resonance imaging study (MRI) performed within two weeks of study drug administration.
  6. If patient received intratumoral chemotherapy or immunotherapy as part of their prior therapy then histological confirmation of recurrence is mandated.
  7. KPS >= 70%.

  8. The following laboratory results:

    • Absolute neutrophil count >= 1500 cells/microliter
    • Platelet count >= 100,000 cells/microliter
    • SGOT <= 2.5 x ULN
    • Serum creatinine <= 1.5 x ULN
  9. Signed informed consent approved by Institutional Review Board.
  10. If sexually active, patients will take contraceptive measures for the duration of the treatment.
  11. For patients on corticosteroids, they must have been on a stable dose 1 week prior to baseline MRI and the dose should not be escalated over entry dose level, if clinically possible.

Exclusion Criteria:

  1. Pregnant or breast feeding women.
  2. Prior treatment with O6-BG plus temozolomide in combination.
  3. Active infection requiring intravenous antibiotics.
  4. Known diagnosis of Human Immunodeficiency Virus (HIV) infection (HIV testing is not mandatory).
  5. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  6. Patients unwilling or unable to comply with the protocol.
  7. Patients who have received stereotactic radiosurgery or brachytherapy as part of their prior therapy.
  8. Comedication that may interfere with study results; eg. immunosuppressive agents other than corticosteroids.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temozolomide + O6BG
Drug: Temozolomide and O6-Benzylguanine
O6BG + Temozolomide
Other Names:
  • temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
best objective response rate
Time Frame: Month 1, 2 and every 2 months thereafter.
Month 1, 2 and every 2 months thereafter.

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety Assessment
Time Frame: Month 1, 2 and every 2 months thereafter
Month 1, 2 and every 2 months thereafter
progression-free survival
Time Frame: every 6 months
every 6 months
overall survival
Time Frame: every 6 months
every 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Keryx / AOI Pharmaceuticals, Inc.

Investigators

  • Study Chair: Jennifer Quinn, MD, Preston Robert Tisch Brain Tumor Center at Duke

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

October 16, 2006

First Submitted That Met QC Criteria

October 16, 2006

First Posted (Estimate)

October 18, 2006

Study Record Updates

Last Update Posted (Estimate)

February 9, 2012

Last Update Submitted That Met QC Criteria

February 7, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • O6BG 202

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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