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

Glioblastoma Multiforme Clinical Trial

Official title:

Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00613093
• Other study ID #: 4260
• Status: Completed
• Phase: Phase 2
• First received: January 29, 2008
• Last updated: July 8, 2014
• Start date: October 2002
• Est. completion date: August 2008

Study information

• Verified date: November 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: August 2008
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Glioma
• Glioblastoma
• Glioblastoma Multiforme
• Glioma

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Health System	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	Keryx / AOI Pharmaceuticals, Inc., National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic evidence of tumor response		6 months	No
Secondary	6 month progression-free survival		6 months	No
Secondary	Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG		6 months	No

External Links

•   The Preston Robert Tisch Brain Tumor Center at DUKE