Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma

NCT00613093 | Completed Phase 2 DMC

• 1 other identifier: 4260
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: To define role of O6-Benzylguanine (BG) in restoring Temodar (temozolomide) sensitivity in patients with Temodar-resistant malignant glioma. To further define toxicity of combo therapy using Temodar + BG.

Conditions

Glioblastoma Multiforme; Anaplastic Glioma

Keywords

Temodar; Temozolomide; O6-BG; O6-Benzylguanine; NSC 637037; Temodar-Resistant Malignant Glioma; Brain tumor; CNS tumor; Cerebral glioblastoma; Anaplastic astrocytomas; Glioma

Outcome Measures

Primary Outcomes (1)

• Radiographic evidence of tumor response

  6 months

Secondary Outcomes (2)

• 6 month progression-free survival

  6 months

• Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG

  6 months

Study Arms (2)

Patients with glioblastoma multiforme

ACTIVE COMPARATOR

Drug: Temodar and O6-Benzylguanine (BG)

Patients with Anaplastic Glioma

ACTIVE COMPARATOR

Drug: Temodar and O6-Benzylguanine (BG)

Interventions

Temodar and O6-Benzylguanine (BG) DRUG

Objectives of study are to define role of BG in restoring Temodar sensitivity in patients with Temodar-resistant malignant glioma and to further define the toxicity of combination therapy using Temodar + BG. 2 separate strata accrued independently of each other: Stratum 1-patients with glioblastoma multiforme (GBM). Stratum 2-patients with anaplastic glioma (AG). BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24 hours. Temodar 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle.

Also known as: Temodar - Temozolomide, O6-Benzylguanine - O6-BG

Patients with Anaplastic Glioma; Patients with glioblastoma multiforme

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients have recurrent/progressive Malignant Glioma (MG). Stereotactic biopsy at time of recurrence/progression is only required if radiation-induced necrosis is suspected
• Patients have MG resistant to Temodar, which is defined as \> or = to 25 percent increase in tumor growth on contrast enhanced MRI/CT within 8 weeks of last dose of Temodar
• Age \> or = to 18 years
• Evidence of measurable enhancing disease on contrast-enhanced MRI, unless medically contraindicated.
• Interval of at least 2 weeks between prior surgical resection/ 4 weeks between prior radiotherapy/chemotherapy, and enrollment on protocol unless there is unequivocal evidence of tumor progression. However, patients treated with chemotherapy agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if less than 4 weeks from last prior dose of chemotherapy
• Karnofsky performance score \> or = to 60 percent
• Hematocrit \> 29 percent, absolute neutrophil count (ANC) \> 1,500 cells/microliter, platelets \> 100,000 cells/microliter
• Serum creatinine \<1.5 mg/dl, Blood Urea Nitrogen (BUN) \<25 mg/dl, Serum Glutamic Oxaloacetic Transaminase (SGOT) \& bilirubin \<1.5 x upper limit of normal (ULN)
• For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, and dose should not be escalated over entry dose level
• Signed informed consent approved by Institutional Review Board (IRB) prior to patient entry
• If sexually active, patients will take contraceptive measures for duration of treatments

You may not qualify if:

• Pregnancy
• Co-medication that may interfere with study results

Sponsors & Collaborators

• Duke University: lead
• Keryx / AOI Pharmaceuticals, Inc.: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Glioma

Interventions

Temozolomide; O(6)-benzylguanine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David A. Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: October 1, 2002
• Primary Completion: March 1, 2006
• Study Completion: August 1, 2008
• Last Updated: July 9, 2014

Record last verified: 2012-11

Locations

US (1)