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

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 anaplastic glioma.

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

Primary outcome:

best objective response rate

occurrence of treatment related AEs

Secondary outcome:

best overall response

progression-free survival

overall survival

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

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