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

Primary Purpose

Glioblastoma Multiforme, Anaplastic Glioma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Temodar and O6-Benzylguanine (BG)
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Temodar, Temozolomide, O6-BG, O6-Benzylguanine, NSC 637037, Temodar-Resistant Malignant Glioma, Brain tumor, CNS tumor, Cerebral glioblastoma, Anaplastic astrocytomas, Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Duke University Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Patients with glioblastoma multiforme

Patients with Anaplastic Glioma

Arm Description

Outcomes

Primary Outcome Measures

Radiographic evidence of tumor response

Secondary Outcome Measures

6 month progression-free survival
Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG

Full Information

First Posted
January 29, 2008
Last Updated
July 8, 2014
Sponsor
Duke University
Collaborators
Keryx / AOI Pharmaceuticals, Inc., National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00613093
Brief Title
Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma
Official Title
Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
March 2006 (Actual)
Study Completion Date
August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Keryx / AOI Pharmaceuticals, Inc., National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients with glioblastoma multiforme
Arm Type
Active Comparator
Arm Title
Patients with Anaplastic Glioma
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Temodar and O6-Benzylguanine (BG)
Other Intervention Name(s)
Temodar - Temozolomide, O6-Benzylguanine - O6-BG
Intervention Description
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.
Primary Outcome Measure Information:
Title
Radiographic evidence of tumor response
Time Frame
6 months
Secondary Outcome Measure Information:
Title
6 month progression-free survival
Time Frame
6 months
Title
Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A. Reardon, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.cancer.duke.edu/btc/
Description
The Preston Robert Tisch Brain Tumor Center at DUKE

Learn more about this trial

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

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