A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
Information source: AOI Pharma, Inc.
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glioma; Astrocytoma; Oligodendroglioma; Oligoastrocytoma
Intervention: Temozolomide and O6-Benzylguanine (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: AOI Pharma, Inc.
Official(s) and/or principal investigator(s):
Jennifer Quinn, MD, Study Chair, Affiliation: Preston Robert Tisch Brain Tumor Center at Duke
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
Official title: A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
Study design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
best objective response rate
occurrence of treatment related AEs
best overall response
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
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
Minimum age: 18 Years.
Maximum age: N/A.
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
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
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
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
8. Comedication that may interfere with study results; eg. immunosuppressive agents other
Locations and Contacts
AOI Pharmaceuticals Investigative Site, Los Angeles, California 90033, United States
AOI Pharmaceuticals Investigative Site, Orlando, Florida 32804, United States
AOI Pharmaceuticals Investigative Site, Evanston, Illinois 60201, United States
AOI Pharmaceuticals Investigative Site, Chicago, Illinois 60611, United States
AOI Pharmaceuticals Investigative Site, Lexington, Kentucky 40536, United States
AOI Pharmaceuticals Investigative Site, Louisville, Kentucky 40202, United States
AOI Pharmaceuticals Investigative Site, Minneapolis, Minnesota 54407, United States
AOI Pharmaceuticals Investigative Site, Durham, North Carolina 27710, United States
AOI Pharmaceuticals Investigative Site, Greenville, South Carolina 29605, United States
AOI Pharmaceuticals Investigative Site, Dallas, Texas 75246, United States
AOI Pharmaceuticals Investigative Site, Houston, Texas 77024, United States
AOI Pharmaceuticals Investigative Site, Salt Lake City, Utah 84132, United States
Starting date: October 2006
Ending date: December 2008
Last updated: April 4, 2008