O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00436436

Purpose

RATIONALE: Drugs used in chemotherapy, such as O(6)-benzylguanine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving O(6)-benzylguanine together with temozolomide works in treating patients with glioblastoma multiforme that did not respond to previous temozolomide and radiation therapy.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: O6-benzylguanine Drug: temozolomide	Phase II

MedlinePlus related topics: Cancer Radiation Therapy

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase 2 Study of O-Benzylguanine (O-BG) and Temozolomide in Patients With Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment With Radiation Therapy and Temozolomide

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Confirmed best objective tumor response rate (complete or partial response) in patients with methylguanine methyltransferase (MGMT)-positive tumors as assessed by immunohistochemistry (IHC) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective tumor response rate in patients with MGMT-negative tumors as assessed by IHC [ Designated as safety issue: No ]
Toxicity as assessed by CTCAE v 3 [ Designated as safety issue: Yes ]
Best overall response [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	December 2006
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the antitumor activity of O6-benzylguanine and temozolomide in patients with temozolomide-resistant methylguanine methyltransferase-positive or -negative glioblastoma multiforme previously treated with radiotherapy.
Determine, preliminarily, the toxicity of this regimen in these patients.

OUTLINE: Patients receive O6-benzylguanine IV over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 6 months.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed glioblastoma multiforme (GBM), including the following:
- Small or large cell GBM
- Gliosarcoma
Temozolomide-resistant disease, as defined by the following:
- Unequivocal evidence of tumor progression after receiving adjuvant temozolomide therapy for 5 consecutive days every 28 days for ≥ 2 courses
Must have failed prior radiotherapy
- Progression must be documented by MRI (while on a stable steroid dose for ≥ 5 days) ≥ 12 weeks after completion of radiotherapy
Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded microscope slides available from diagnosis

PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
Life expectancy > 8 weeks
WBC ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10 g/dL (transfusion allowed)
AST < 2 times upper limit of normal (ULN)
Bilirubin < 2 times ULN
Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
No significant medical illness that, in the opinion of the investigator, would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No significant active cardiac, hepatic, renal, or psychiatric disease
No other known active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix
No active infection requiring IV antibiotics
No disease that would obscure toxicity or alter drug metabolism

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior temozolomide
Prior resection of recurrent or progressive tumor allowed if all the following criteria are met:
- Recovered from prior surgery
- Residual disease after resection of recurrent tumor by CT scan or MRI (while on a stable steroid dose for ≥ 5 days) ≤ 96 hours OR ≥ 4 weeks after surgery
At least 12 weeks since prior radiotherapy
No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel wafers] or nitrosoureas)
No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436436

Locations

United States, Maryland
NCI - Neuro-Oncology Branch
Bethesda, Maryland, United States, 20892-8200
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Howard A. Fine, MD

NCI - Neuro-Oncology Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000529875, NCI-07-C-0052, AOI-NCI-07-C-0052
Study First Received:	February 15, 2007
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00436436 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult giant cell glioblastoma
adult gliosarcoma
recurrent adult brain tumor
adult glioblastoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Temozolomide
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Glioma
Glioblastoma Multiforme
Gliosarcoma
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

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

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

ClinicalTrials.gov processed this record on May 07, 2009