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

• Status: Terminated
• Trial end date: 2009-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Keryx / AOI Pharmaceuticals, Inc.
• Treatments: Dacarbazine; O(6)-benzylguanine; Temozolomide

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.