O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors

NCT00275002 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2012-03050PBTC-015NCI-06-C-0089NCI-P6692CDR0000455561
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 11

Brief Summary

This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-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. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent childhood brain stem glioma; recurrent childhood brain tumor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Objective Response (Complete Response or Partial Response)

  The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.

  Week 8, 16, 24, 32, and 40 after starting therapy

Secondary Outcomes (1)

• Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide

  From day 1 of therapy up to 49 months

Study Arms (1)

O6-BG and TMZ

EXPERIMENTAL

O6-benzylguanine (O6-BG) and temozolomide (TMZ)

Drug: O6-benzylguanine; Drug: temozolomide

Interventions

O6-benzylguanine DRUG

Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m\^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy.

O6-BG and TMZ

temozolomide DRUG

Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m\^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses.

Also known as: Temodar

O6-BG and TMZ

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions
• Age: 21 years of age or less
• Performance status: Karnofsky 60-100% (for patients \> 16 years of age) or Lansky 60-100% (for patients ≤ 16 years of age)
• Life expectancy: Not specified
• Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count \> 1,500/mm\^3, platelet count \> 100,000/mm\^3 (unsupported), hemoglobin \> 8 g/dL (may be supported), and absolute lymphocyte count ≥ 500/mm\^3
• Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN, and no overt hepatic disease
• Renal: Participants must have creatinine clearance ≥ 60 mL/min or creatinine based on age as follows: no greater than 0.8 mg/dL (for patients ≤ 5 years of age), no greater than 1.0 mg/dL (for patients 6 to 10 years of age), no greater than 1.2 mg/dL (for patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients \> 15 years of age). There must be no overt renal disease
• Cardiovascular: Must have no overt cardiac disease
• Pulmonary: Must have no overt pulmonary disease
• Other: Female participants of childbearing potential must have a negative pregnancy test prior to study registration, and must avoid breast-feeding. Female and male participants of childbearing or child-fathering potential must use effective contraception
• Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow transplantation and at least 3 months since prior autologous bone marrow or stem cell transplantation
• Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or erythropoietin)
• Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas. Must have received last dose of nonmyelosuppressive investigational agents or anticancer drugs ≥ 7 days prior to study registration. Participants who have received prior temozolomide are eligible
• Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed
• Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and local irradiation to the primary tumor ≥ 12 weeks prior to study registration

You may not qualify if:

• Must not have history of severe toxicity (≥ grade 3) associated with temozolomide
• Must not be receiving other concurrent anticancer or investigational therapy
• Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
• Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease
• Must not be HIV positive

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

O(6)-benzylguanine; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dana Wallace
• Organization: Pediatric Brain Tumor Consortium

dana.wallace@stjude.org

901-595-2617

Study Officials

• Katherine Warren, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: February 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 11, 2022
• Results First Posted: August 9, 2011

Record last verified: 2022-01

Locations

US (11)