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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00436436
First received: February 15, 2007
Last updated: December 13, 2008
Last verified: October 2008
  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 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: Howard A. Fine, MD NCI - Neuro-Oncology Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00436436     History of Changes
Other Study ID Numbers: CDR0000529875, NCI-07-C-0052, AOI-NCI-07-C-0052
Study First Received: February 15, 2007
Last Updated: December 13, 2008
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

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Dacarbazine
O(6)-benzylguanine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014