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Ph I 5-day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM

Primary Purpose

Glioblastoma, Gliosarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Temodar and O6-Benzylguanine
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Gliosarcoma, GBM, Temodar, Temozolomide, O6-BG, O6-Benzylguanine, Recurrent GBM, Progressive GBM, Brain tumor, Malignant glioma, Neulasta, Pegfilgrastim

Eligibility Criteria

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

Inclusion Criteria:

  • Pts have histologically proven supratentorial GBM
  • Pts have recurrent/progressive MG. If pt received stereotactic radiosurgery / brachytherapy as part of their prior therapy, then histologic confirmation of recurrence/metabolic imaging consistent w recurrent tumor is recommended but not mandated
  • There must be measurable disease on contrast-enhanced magnetic resonance imaging study / CT scan performed <2wks of study drug administration
  • Interval of >12 wks between completion of XRT & enrollment on protocol
  • Interval of >4 wks between prior chemo & enrollment on protocol unless there is unequivocal evidence of tumor progression
  • Interval of >2 wks between prior surgical resection & enrollment on protocol unless there is unequivocal evidence of tumor progression
  • Age >18 yrs
  • KPS >70 percent
  • Following baseline study will be required <1wk of study drug administration: serum creatinine < 1.5 x ULN & Hematologic Status
  • Following baseline studies will be required <1wk of study drug administration: absolute neutrophil count >2000 cells/microliter; platelet count >125,000 cells/microliter
  • Following baseline studies will be required <1 wk of study drug administration: serum SGOT & total bilirubin < 2.5 x ULN
  • Signed informed consent, approved by IRB, will be obtained prior to initiating treatment
  • Pts w Reproductive Potential: Pts must agree to practice effective birth control measures while on study & for 2 months after completing therapy

Exclusion Criteria:

  • Pregnant/breast feeding women/ women/men w reproductive potential not practicing adequate contraception. Therapy may be associated w potential toxicity to fetus/child that exceeds mini risks necessary to meet health needs of mother
  • Prior treatment w O6-BG + Temozolomide in combo
  • Active infection requiring intravenous antibiotics
  • Known diagnosis of HIV infection
  • Pts w history of another primary malignancy that is currently clinically significant/currently requires active intervention
  • Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition
  • Pts who have received investigational drugs <2 wks prior to start on study drug/have not recovered from side effects of such therapy.

Sites / Locations

  • Duke University Health System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

1

2

3

Arm Description

Schedule 1

Schedule 2

Schedule 2, Neulasta-supported

Outcomes

Primary Outcome Measures

Dose limiting toxicity

Secondary Outcome Measures

Progression-free survival

Full Information

First Posted
January 29, 2008
Last Updated
July 15, 2014
Sponsor
Duke University
Collaborators
Schering-Plough, Keryx / AOI Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00612989
Brief Title
Ph I 5-day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM
Official Title
Phase I Trial of a 5-day Regimen of Temodar Plus O6-Benzylguanine (O6-BG) in the Treatment of Patients With Recurrent / Progressive Glioblastoma Multiforme
Study Type
Interventional

2. Study Status

Record Verification Date
January 2009
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Duke University
Collaborators
Schering-Plough, Keryx / AOI Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary objectives To determine maxi tolerated dose of Temodar® in combo w O6-benzylguanine administered for 5 consecutive days in pts w progressive/recurrent GBM To characterize toxicity associated w Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM To determine Neulasta®-supported MTD defined as the MTD of Temodar® in combo with O6-BG administered for 5 days while receiving Neulasta® once per treatment cycle between days 7 & 14 in pts w progressive/recurrent GBM To obtain preliminary response rates of Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM
Detailed Description
1 primary objective is to determine maximum tolerated dose of Temodar in combo w O6-benzylguanine administered for 5 consecutive days in pts w progressive/recurrent GBM. Another primary objective is to characterize toxicity associated w Temozolomide in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM. 3rd primary objective is to determine Neulasta-supported MTD defined as MTD of Temozolomide in combo w O6-BG administered for 5 days while receiving Neulasta once per treatment cycle between days 7 & 14 in pts w progressive/recurrent GBM. Secondary objective is to obtain preliminary response rates of Temodar in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM. Population is Glioblastoma. O6-BG Administration: O6-BG 120mg/m2 administered intravenously over 1 hr followed by continuous infusion of O6-BG at 30mg/m2/day for 5 consecutive days. Every 48hrs repeat dose of 120mg/m2 over 1hr administered for total of 3 doses. Temodar Administration: Temodar administered orally, in fasting state within 60 mins of end of 1st 1-hr infusion of O6-BG & then every 24 hrs during continuous infusion of O6-BG. Temozolomide administered on day 1 of treatment cycle and every 24 hrs thereafter for 5 days w treatment cycles repeated every 28 days. Body surface area calculated at beginning of each cycle will be used to calculate daily dose of Temozolomide administered for that cycle. Neulasta Administration. Neulasta administered by subcutaneous injection in 0.6mL pre-filled syringe containing 6mg of pegfilgrastim. It will be administered once per chemotherapy cycle between days 7 & 14. Neulasta should not be administered in period between 14 days before & 24hrs after administration of cytotoxic chemo including Temozolomide. Data Analysis will be conducted by Biostatistics department of Duke.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma
Keywords
Glioblastoma, Gliosarcoma, GBM, Temodar, Temozolomide, O6-BG, O6-Benzylguanine, Recurrent GBM, Progressive GBM, Brain tumor, Malignant glioma, Neulasta, Pegfilgrastim

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Schedule 1
Arm Title
2
Arm Type
Experimental
Arm Description
Schedule 2
Arm Title
3
Arm Type
Experimental
Arm Description
Schedule 2, Neulasta-supported
Intervention Type
Drug
Intervention Name(s)
Temodar and O6-Benzylguanine
Other Intervention Name(s)
Temodar, Temozolomide, O6-BG, O6-Benzylguanine, NSC637037, Neulasta, Pegfilgrastim
Intervention Description
O6-BG 120mg/m2 administered intravenously over 1 hr followed by continuous infusion of O6-BG at 30 mg/m2/day for 5 consecutive days. Every 48 hrs repeat dose of 120 mg/m2 over 1 hr administered for total of 3 doses. Temodar administered orally, in fasting state within 60 minutes of end of 1st 1-hr infusion of O6-BG & then every 24 hrs during continuous infusion of O6-BG. Temodar administered on day 1 of treatment cycle & every 24 hrs thereafter for 5 days with treatment cycles repeated every 28 days. Pts must fast for minimum of 1 hr prior to administration of each dose of Temodar & continue fasting 2 hrs after administration of each Temodar dose.
Primary Outcome Measure Information:
Title
Dose limiting toxicity
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pts have histologically proven supratentorial GBM Pts have recurrent/progressive MG. If pt received stereotactic radiosurgery / brachytherapy as part of their prior therapy, then histologic confirmation of recurrence/metabolic imaging consistent w recurrent tumor is recommended but not mandated There must be measurable disease on contrast-enhanced magnetic resonance imaging study / CT scan performed <2wks of study drug administration Interval of >12 wks between completion of XRT & enrollment on protocol Interval of >4 wks between prior chemo & enrollment on protocol unless there is unequivocal evidence of tumor progression Interval of >2 wks between prior surgical resection & enrollment on protocol unless there is unequivocal evidence of tumor progression Age >18 yrs KPS >70 percent Following baseline study will be required <1wk of study drug administration: serum creatinine < 1.5 x ULN & Hematologic Status Following baseline studies will be required <1wk of study drug administration: absolute neutrophil count >2000 cells/microliter; platelet count >125,000 cells/microliter Following baseline studies will be required <1 wk of study drug administration: serum SGOT & total bilirubin < 2.5 x ULN Signed informed consent, approved by IRB, will be obtained prior to initiating treatment Pts w Reproductive Potential: Pts must agree to practice effective birth control measures while on study & for 2 months after completing therapy Exclusion Criteria: Pregnant/breast feeding women/ women/men w reproductive potential not practicing adequate contraception. Therapy may be associated w potential toxicity to fetus/child that exceeds mini risks necessary to meet health needs of mother Prior treatment w O6-BG + Temozolomide in combo Active infection requiring intravenous antibiotics Known diagnosis of HIV infection Pts w history of another primary malignancy that is currently clinically significant/currently requires active intervention Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition Pts who have received investigational drugs <2 wks prior to start on study drug/have not recovered from side effects of such therapy.
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 I 5-day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM

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