Trial | NCT00613093  Report issue

Title

Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma
Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma

  • Phase

    Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    67
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.
2 separate strata accrued independently of each other: Stratum 1-patients with Glioblastoma Multiforme (GBM). Stratum 2-patients with Anaplastic Glioma [anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed (AA and AO)] .

BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24hrs. Temozolomide 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.

Temodar has been well tolerated by both adults and children with most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, hepatotoxicity, anorexia, fatigue and hyperglycemia. Hypersensitivity reactions have not yet been noted with Temodar. As in the case with many anti-cancer drugs, Temodar may be carcinogenic. BG toxicities include agitation, lethargy, nausea, vomiting, rapid heart rate, elevated liver functions, & leukemia; but, not with BG as single agent. Transient lymphopenia has been seen with BG as single agent.
Study Started
Oct 31
2002
Primary Completion
Mar 31
2006
Study Completion
Aug 31
2008
Last Update
Jul 09
2014
Estimate

Drug Temodar and O6-Benzylguanine (BG)

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.

  • Other names: Temodar - Temozolomide, O6-Benzylguanine - O6-BG

Patients with glioblastoma multiforme Active Comparator

Patients with Anaplastic Glioma Active Comparator

Criteria 

Inclusion Criteria:

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

Exclusion criteria:

Pregnancy
Co-medication that may interfere with study results
No Results Posted