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

NCT00436436 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: 070052NCI-07-C-0052AOI-NCI-07-C-0052CDR0000529875
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Confirmed Best Objective Tumor Response Rate (Complete or Partial Response) in Patients With Methylguanine Methyltransferase (MGMT)-Positive Tumors as Assessed by Immunohistochemistry (IHC)

  The date of response will be the date the response is first radiographically documented following initiation of therapy (typically, the date of the actual imaging modality). Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions.

  2-4 weeks

Secondary Outcomes (5)

• Objective Tumor Response Rate in Patients With Methylguanine Methyltransferase (MGMT)-Negative Tumors as Assessed by Immunohistochemistry (IHC)

  2-4 weeks

• Toxicity as Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v 3)

  18 months and 4 days

• Best Overall Response

  up to 2 years

• Progression-free Survival

  up to 2 years

• Overall Survival

  up to 2 years

Study Arms (1)

O6-benzylguanine & Temozolomide in Glioblastoma

EXPERIMENTAL

Patients receive O6-benzylguanine intravenous 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.

Drug: O6-benzylguanine; Drug: temozolomide

Interventions

O6-benzylguanine DRUG

Also known as: 06-BG

O6-benzylguanine & Temozolomide in Glioblastoma

temozolomide DRUG

Also known as: Temodar

O6-benzylguanine & Temozolomide in Glioblastoma

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 * White blood cell (WBC) ≥ 3,000/mm(³) * Absolute neutrophil count ≥ 1,500/mm(³) * Platelet count ≥ 100,000/mm(³) * Hemoglobin ≥ 10 g/dL (transfusion allowed) * Aspartate aminotransaminase (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 intravenous (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 computed tomography (CT) scan or magnetic resonance imaging (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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

NCI - Neuro-Oncology Branch

Bethesda, Maryland, 20892-8200, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

O(6)-benzylguanine; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Dr. Howard A. Fine is no longer with the National Cancer Institute (NCI). For historical reasons, he is listed as the (original principal investigator) study official for this study.

Results Point of Contact

• Title: Dr. Mark Gilbert
• Organization: National Cancer Institute

gilbertmr@mail.nih.gov

301-402-6383

Study Officials

• Howard A Fine, M.D.

  NCI - Neuro-Oncology Branch

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Branch Chief, Neuro-Oncology Branch

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: November 13, 2006
• Primary Completion: March 15, 2010
• Study Completion: April 14, 2010
• Last Updated: March 28, 2017
• Results First Posted: March 28, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)