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| ID | Type | Description | Link |
|---|---|---|---|
| POG-9870 | |||
| CDR0000066891 | Registry Identifier | PDQ (Physician Data Query) |
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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.
OBJECTIVES:
I. Determine the maximum tolerated dose and the dose limiting toxicity of carmustine administered after O6-benzylguanine in children with refractory primary CNS tumors.
II. Determine a safe and tolerable dose of carmustine administered after O6-benzylguanine to be used in phase II studies.
III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, O6-benzyl-8-oxoguanine, in these patients.
IV. Seek preliminary evidence of antitumor activity of this regimen in these patients.
V. Evaluate the acute and chronic toxicities, and describe cumulative toxicity, in patients treated with multiple courses of this regimen.
OUTLINE: This is a dose escalation study of carmustine.
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. Patients are followed every 6 months for 4 years, then annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| O6-benzylguanine | Drug |
| ||
| carmustine |
DISEASE CHARACTERISTICS:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Denise Adams, MD | University of Vermont | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States | ||
| University of California San Diego Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17941066 | Result | 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. |
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|
| La Jolla |
| California |
| 92093-0658 |
| United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027-0700 | United States |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles | California | 90095-1781 | United States |
| City of Hope National Medical Center | Los Angeles | California | 91010 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| UCSF Cancer Center and Cancer Research Institute | San Francisco | California | 94115-0128 | United States |
| Stanford University Medical Center | Stanford | California | 94305-5408 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010-2970 | United States |
| University of Florida Health Science Center | Gainesville | Florida | 32610-0296 | United States |
| Emory University Hospital - Atlanta | Atlanta | Georgia | 30322 | United States |
| Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago | Illinois | 60611 | United States |
| Children's Memorial Hospital, Chicago | Chicago | Illinois | 60614 | United States |
| Indiana University Cancer Center | Indianapolis | Indiana | 46202-5265 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160-7357 | United States |
| Johns Hopkins Oncology Center | Baltimore | Maryland | 21231 | United States |
| Boston Floating Hospital Infants and Children | Boston | Massachusetts | 02111 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109-0752 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| University of Minnesota Cancer Center | Minneapolis | Minnesota | 55455 | United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216-4505 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Cardinal Glennon Children's Hospital | St Louis | Missouri | 63104 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Cancer Institute of New Jersey | New Brunswick | New Jersey | 08901 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263-0001 | United States |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York | New York | 10016 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
| Columbia Presbyterian Hospital | New York | New York | 10032 | United States |
| State University of New York - Upstate Medical University | Syracuse | New York | 13210 | United States |
| Graham Children's Health Center | Asheville | North Carolina | 28801 | United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| Children's Hospital Medical Center - Cincinnati | Cincinnati | Ohio | 45229-3039 | United States |
| Children's Hospital of Columbus | Columbus | Ohio | 43205-2696 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73190 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425-0721 | United States |
| Vanderbilt Cancer Center | Nashville | Tennessee | 37232-6838 | United States |
| Simmons Cancer Center - Dallas | Dallas | Texas | 75235-9154 | United States |
| Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | 76104 | United States |
| Texas Children's Cancer Center | Houston | Texas | 77030-2399 | United States |
| University of Texas - MD Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78284-7811 | United States |
| Primary Children's Medical Center | Salt Lake City | Utah | 84113 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| University of Wisconsin Comprehensive Cancer Center | Madison | Wisconsin | 53792 | United States |
| Midwest Children's Cancer Center | Milwaukee | Wisconsin | 53226 | United States |
| Royal Children's Hospital | Parkville | Victoria | 3052 | Australia |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6001 | Australia |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Montreal Children's Hospital | Montreal | Quebec | H3H 1P3 | Canada |
| Hopital Sainte Justine | Montreal | Quebec | H3T 1C5 | Canada |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009837 | Oligodendroglioma |
| D016545 | Choroid Plexus Neoplasms |
| D020339 | Optic Nerve Glioma |
| D001254 | Astrocytoma |
| D008527 | Medulloblastoma |
| C531673 | Familial ependymoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D002551 | Cerebral Ventricle Neoplasms |
| D001932 | Brain Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D019574 | Optic Nerve Neoplasms |
| D003390 | Cranial Nerve Neoplasms |
| D010524 | Peripheral Nervous System Neoplasms |
| D003389 | Cranial Nerve Diseases |
| D009901 | Optic Nerve Diseases |
| D005128 | Eye Diseases |
| D018242 | Neuroectodermal Tumors, Primitive |
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| ID | Term |
|---|---|
| C064976 | O(6)-benzylguanine |
| D002330 | Carmustine |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
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