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

Sponsor:	Duke University
Collaborators:	Keryx / AOI Pharmaceuticals, Inc. National Institutes of Health (NIH)
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00613093

Purpose

Objectives:

To define role of O6-Benzylguanine (BG) in restoring Temodar sensitivity in pts w Temodar-resistant malignant glioma.

To further define toxicity of combo therapy using Temodar + BG.

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

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Official Title:	Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

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

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Radiographic evidence of tumor response [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

6 month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Relationship between tumor AGT at original diagnosis & response to Temozolomide + O6-BG [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	64
Study Start Date:	October 2002
Study Completion Date:	July 2008
Primary Completion Date:	November 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Pts w GBM	Drug: Temodar and O6-Benzylguanine Objectives of study are to define role of O6-BG in restoring Temozolomide sensitivity in pts w Temozolomide-resistant MG & to further define toxicity of combo therapy using Temozolomide + BG. 2 separate strata accrued independently of each other: Stratum 1-pts w GBM. Stratum 2-pts w anaplastic astrocytoma. O6-BG at 120mg/m2 administered intravenously over 1hr followed immediately by 48hr infusion at 30mg/m2/24 hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60mins of end of 1hr administration of O6-BG infusion. Treatment cycles may be repeated every 28 days following dose of Temozolomide from previous cycle.
2: Experimental Pts w AA	Drug: Temodar and O6-Benzylguanine Objectives of study are to define role of O6-BG in restoring Temozolomide sensitivity in pts w Temozolomide-resistant MG & to further define toxicity of combo therapy using Temozolomide + BG. 2 separate strata accrued independently of each other: Stratum 1-pts w GBM. Stratum 2-pts w anaplastic astrocytoma. O6-BG at 120mg/m2 administered intravenously over 1hr followed immediately by 48hr infusion at 30mg/m2/24 hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60mins of end of 1hr administration of O6-BG infusion. Treatment cycles may be repeated every 28 days following dose of Temozolomide from previous cycle.

Arms

Assigned Interventions

1: Experimental

Pts w GBM

Drug: Temodar and O6-Benzylguanine

Objectives of study are to define role of O6-BG in restoring Temozolomide sensitivity in pts w Temozolomide-resistant MG & to further define toxicity of combo therapy using Temozolomide + BG. 2 separate strata accrued independently of each other: Stratum 1-pts w GBM. Stratum 2-pts w anaplastic astrocytoma.

O6-BG at 120mg/m2 administered intravenously over 1hr followed immediately by 48hr infusion at 30mg/m2/24 hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60mins of end of 1hr administration of O6-BG infusion. Treatment cycles may be repeated every 28 days following dose of Temozolomide from previous cycle.

2: Experimental

Pts w AA

Drug: Temodar and O6-Benzylguanine

Objectives of study are to define role of O6-BG in restoring Temozolomide sensitivity in pts w Temozolomide-resistant MG & to further define toxicity of combo therapy using Temozolomide + BG. 2 separate strata accrued independently of each other: Stratum 1-pts w GBM. Stratum 2-pts w anaplastic astrocytoma.

O6-BG at 120mg/m2 administered intravenously over 1hr followed immediately by 48hr infusion at 30mg/m2/24 hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60mins of end of 1hr administration of O6-BG infusion. Treatment cycles may be repeated every 28 days following dose of Temozolomide from previous cycle.

Detailed Description:

2 separate strata accrued independently of each other: Stratum 1-pts w GM. Stratum 2-pts w AA.

O6-BG at 120mg/m2 administered intravenously over 1hr followed immediately by 48hr infusion at 30mg/m2/ 24hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60mins of end of 1hr administration of O6-BG infusion. Treatment cycles may be repeated every 28 days following dose of Temozolomide from previous cycle.

Temozolomide has been well tolerated by both adults & children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea & 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 Temozolomide. As in the case w many anti-cancer drugs, Temozolomide may be carcinogenic. O6-BG toxicities include agitation, lethargy, nausea, vomiting, rapid heart rate, elevated liver functions, & leukemia; but, not with O6-BG as single agent. Transient lymphopenia has been seen w O6-BG as single agent.

Eligibility

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

Criteria

Inclusion Criteria:

Pts have recurrent/progressive MG. Stereotactic biopsy at time of recurrence/progression is only required if radiation-induced necrosis is suspected
Pt have MG resistant to Temozolomide, which is defined as >25 percent increase in tumor growth on contrast enhanced MRI/CT <8 wks of last dose of Temozolomide-Age >18 yrs
Evidence of measurable enhancing disease on contrast-enhanced MRI, unless medically contraindicated.
Interval of >2 wks between prior surgical resection/ 4wks between prior XRT/chemo, & enrollment on protocol unless there is unequivocal evidence of tumor progression. However, pts treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if <4 wks from last prior dose of chemo
Karnofsky performance score >60 percent
Hematocrit > 29 percent, ANC > 1,500 cells/microliter, platelets > 100,000 cells/microliter
Serum creatinine <1.5 mg/dl, BUN <25 mg/dl, serum SGOT & bilirubin <1.5 x ULN
For pts on corticosteroids, they must have been on stable dose for 1wk prior to entry, if clinically possible, & dose should not be escalated over entry dose level
Signed informed consent approved by IRB prior to pt entry
If sexually active, pts will take contraceptive measures for duration of treatments

Exclusion criteria:

Pregnancy
Co-medication that may interfere w study results

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00613093

Locations

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

Sponsors and Collaborators

Duke University

Keryx / AOI Pharmaceuticals, Inc.

National Institutes of Health (NIH)

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:	4260
Study First Received:	January 29, 2008
Last Updated:	January 22, 2009
ClinicalTrials.gov Identifier:	NCT00613093 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Duke University:

Temodar
Temozolomide
O6-BG
O6-Benzylguanine
NSC 637037
Temodar-Resistant Malignant Glioma

Brain tumor
CNS tumor
Cerebral glioblastoma
Anaplastic astrocytomas
Glioma

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 30, 2009