O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

NCT00003765 | Completed Phase 1

• 3 other identifiers: NCI-2012-01842POG-9870CDR0000066891
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 56

Brief Summary

Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Conditions

Brain and Central Nervous System Tumors

Keywords

childhood craniopharyngioma; childhood central nervous system germ cell tumor; childhood oligodendroglioma; childhood choroid plexus tumor; recurrent childhood brain stem glioma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood visual pathway glioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood medulloblastoma; recurrent childhood ependymoma

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover.

Drug: O6-benzylguanine; Drug: carmustine

Interventions

O6-benzylguanine DRUG

Arm I

carmustine DRUG

Arm I

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically proven CNS tumor that is refractory to conventional therapy or for which no effective therapy is known * Histological requirement may be waived for brainstem and optic gliomas * Stratum 2: No bone marrow involvement PATIENT CHARACTERISTICS: * Age: 21 and under * Performance status: Karnofsky 50-100% OR Lansky 50-100% * Life expectancy: At least 8 weeks * Absolute neutrophil count at least 1500/mm3 * Platelet count at least 100,000/mm3 (stratum 2: at least 125,000/mm3) * Hemoglobin at least 8 g/dL * Bilirubin less than 1.5 mg/dL * SGOT/SGPT no greater than 2.5 times normal * Creatinine or GFR normal for age * If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO test * Neurologic deficits must be stable for at least 2 weeks prior to study * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after study PRIOR CONCURRENT THERAPY: * At least 7 days since prior biologic therapy or immunotherapy and recovered * At least 6 months since prior bone marrow transplant (stratum 1 only) * At least 7 days since prior growth factors * No concurrent filgrastim (G-CSF) prophylaxis * Stratum 2: No prior bone marrow transplantation * At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) and recovered * Stratum 2: No greater than 2 prior chemotherapy regimens * No prior nitrosourea therapy * If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks prior to study * At least 2 weeks since prior local palliative radiotherapy (small port) * At least 6 months since prior substantial bone marrow radiation, total body irradiation, hemipelvic radiotherapy, or total abdominal/pelvic/chest or mantle/Y ports radiotherapy * Recovered from prior radiotherapy * Stratum 2: No prior central axis radiation * No other concurrent anticancer 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 (56)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

City of Hope National Medical Center

Los Angeles, California, 91010, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

Children's National Medical Center

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

Location

University of Florida Health Science Center

Gainesville, Florida, 32610-0296, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

Children's Memorial Hospital, Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5265, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231, United States

Location

Boston Floating Hospital Infants and Children

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0752, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Columbia Presbyterian Hospital

New York, New York, 10032, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Graham Children's Health Center

Asheville, North Carolina, 28801, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Columbus

Columbus, Ohio, 43205-2696, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73190, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

Vanderbilt Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Simmons Cancer Center - Dallas

Dallas, Texas, 75235-9154, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030-2399, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM; Children's Oncology Group. Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer. 2008 Mar;50(3):549-53. doi: 10.1002/pbc.21362.

  PMID: 17941066 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Oligodendroglioma; Choroid Plexus Neoplasms; Optic Nerve Glioma; Astrocytoma; Medulloblastoma; Familial ependymoma

Interventions

O(6)-benzylguanine; Carmustine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Denise Adams, MD

  University of Vermont

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: April 27, 2004
• Study Start: May 1, 1999
• Primary Completion: March 1, 2006
• Last Updated: February 5, 2013

Record last verified: 2007-10

Locations

US (51); AU (2); CA (3)