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

Primary Purpose

Glioma, Astrocytoma, Oligodendroglioma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Temozolomide and O6-Benzylguanine
Sponsored by
Keryx / AOI Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma focused on measuring temozolomide resistant, anaplastic glioma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma

Eligibility Criteria

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

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.

Sites / Locations

  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site
  • AOI Pharmaceuticals Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide + O6BG

Arm Description

Outcomes

Primary Outcome Measures

best objective response rate

Secondary Outcome Measures

Safety Assessment
progression-free survival
overall survival

Full Information

First Posted
October 16, 2006
Last Updated
February 7, 2012
Sponsor
Keryx / AOI Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00389090
Brief Title
A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
Official Title
A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Terminated
Why Stopped
AOI Pharma terminated the license agreement. IND Transferred to NCI
Study Start Date
October 2006 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Keryx / AOI Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Astrocytoma, Oligodendroglioma, Oligoastrocytoma
Keywords
temozolomide resistant, anaplastic glioma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide + O6BG
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Temozolomide and O6-Benzylguanine
Other Intervention Name(s)
temodar
Intervention Description
O6BG + Temozolomide
Primary Outcome Measure Information:
Title
best objective response rate
Time Frame
Month 1, 2 and every 2 months thereafter.
Secondary Outcome Measure Information:
Title
Safety Assessment
Time Frame
Month 1, 2 and every 2 months thereafter
Title
progression-free survival
Time Frame
every 6 months
Title
overall survival
Time Frame
every 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologically documented anaplastic glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or mixed anaplastic oligoastrocytoma). Temozolomide-resistant defined as patients who have progressed while receiving or within 8 weeks of completing the last dose of temozolomide. Disease progression >= 12 weeks after the completion of any radiotherapy. 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. Bi-dimensionally measurable disease on contrast-enhanced magnetic resonance imaging study (MRI) performed within two weeks of study drug administration. If patient received intratumoral chemotherapy or immunotherapy as part of their prior therapy then histological confirmation of recurrence is mandated. KPS >= 70%. 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 Signed informed consent approved by Institutional Review Board. If sexually active, patients will take contraceptive measures for the duration of the treatment. 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: Pregnant or breast feeding women. Prior treatment with O6-BG plus temozolomide in combination. Active infection requiring intravenous antibiotics. Known diagnosis of Human Immunodeficiency Virus (HIV) infection (HIV testing is not mandatory). Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention. Patients unwilling or unable to comply with the protocol. Patients who have received stereotactic radiosurgery or brachytherapy as part of their prior therapy. Comedication that may interfere with study results; eg. immunosuppressive agents other than corticosteroids.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Quinn, MD
Organizational Affiliation
Preston Robert Tisch Brain Tumor Center at Duke
Official's Role
Study Chair
Facility Information:
Facility Name
AOI Pharmaceuticals Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
54407
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
AOI Pharmaceuticals Investigative Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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