Clinical trial NCT00389090: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioma
Astrocytoma
Oligodendroglioma
Oligoastrocytoma
Keywords: temozolomide resistant
anaplastic glioma
anaplastic astrocytoma
anaplastic oligodendroglioma
anaplastic oligoastrocytoma
Lead sponsor: Keryx / AOI Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2006-10-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: best objective response rate
timeFrame: Month 1, 2 and every 2 months thereafter.
Secondary outcomes:
measure: Safety Assessment
timeFrame: Month 1, 2 and every 2 months thereafter
measure: progression-free survival
timeFrame: every 6 months
measure: overall survival
timeFrame: every 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Orlando
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Chicago
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Illinois
city: Evanston
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Illinois
city: Lexington
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Kentucky
city: Minneapolis
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Minnesota
city: Durham
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: North Carolina
city: Greenville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: South Carolina
city: Dallas
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Texas
city: Houston
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Utah
Study officials:
affiliation: Preston Robert Tisch Brain Tumor Center at Duke
name: Jennifer Quinn, MD
role: STUDY_CHAIR
References: