Ph I 5-Day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM - Full Text View

Sponsor:	Duke University
Collaborators:	Schering-Plough Keryx / AOI Pharmaceuticals, Inc.
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00612989

Purpose

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

Condition	Intervention	Phase
Glioblastoma Gliosarcoma	Drug: Temodar and O6-Benzylguanine	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

Drug Information available for: O(6)-Benzylguanine Temozolomide Pegfilgrastim

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Dose limiting toxicity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	February 2005
Study Completion Date:	July 2008
Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Schedule 1	Drug: Temodar and O6-Benzylguanine 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.
2: Experimental Schedule 2	Drug: Temodar and O6-Benzylguanine 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.
3: Experimental Schedule 2, Neulasta-supported	Drug: Temodar and O6-Benzylguanine 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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612989

Locations

United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Schering-Plough

Keryx / AOI Pharmaceuticals, Inc.

Investigators

Principal Investigator:

David A. Reardon, MD

Duke University Health System

More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at DUKE This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke University Health System ( David A. Reardon, MD )
Study ID Numbers:	00004058, 6788
Study First Received:	January 29, 2008
Last Updated:	January 22, 2009
ClinicalTrials.gov Identifier:	NCT00612989 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Duke University:

Glioblastoma
Gliosarcoma
GBM
Temodar
Temozolomide
O6-BG
O6-Benzylguanine

Recurrent GBM
Progressive GBM
Brain tumor
Malignant glioma
Neulasta
Pegfilgrastim

Additional relevant MeSH terms:

Glioblastoma
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Temozolomide
Pharmacologic Actions
Neuroectodermal Tumors

Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Glioma
Gliosarcoma
Neoplasms, Neuroepithelial
Alkylating Agents
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 09, 2009