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

This study is no longer recruiting patients.

Sponsors and Collaborators: National Cancer Institute (NCI)
Pediatric Oncology Group
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: 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. PURPOSE: Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors.

Condition Treatment or Intervention Phase
recurrent childhood brain stem glioma
childhood choroid plexus tumor
recurrent childhood visual pathway glioma
recurrent childhood cerebral astrocytoma
childhood craniopharyngioma
recurrent childhood cerebellar astrocytoma
childhood central nervous system germ cell tumor
recurrent childhood ependymoma
recurrent childhood supratentorial primitive neuroectodermal and pineal tumors
recurrent childhood medulloblastoma
Childhood Oligodendroglioma
 Drug: carmustine
 Drug: O6-benzylguanine
Phase I

MedlinePlus related topics:  Brain Cancer;   Cancer;   Cancer Alternative Therapy

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of O6-Benzylguanine and Carmustine in Children With Refractory CNS Tumors

Further Study Details: 

Study start: May 1999

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.

PROTOCOL 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.

PROJECTED ACCRUAL: Approximately 3-36 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

--Prior/Concurrent Therapy--

  • Biologic 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
  • Chemotherapy: 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
  • Endocrine therapy: If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks prior to study
  • Radiotherapy: 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
  • Surgery: Not specified
  • Other: No other concurrent anticancer or investigational agents

--Patient Characteristics--

  • Age: 21 and under
  • Performance status: Karnofsky 50-100% OR Lansky 50-100%
  • Life expectancy: At least 8 weeks
  • Hematopoietic: 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
  • Hepatic: Bilirubin less than 1.5 mg/dL; SGOT/SGPT no greater than 2.5 times normal
  • Renal: Creatinine or GFR normal for age
  • Pulmonary: If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO test
  • Other: 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

Location Information


Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States

      Children's Hospital of Orange County, Orange,  California,  92868,  United States

      City of Hope National Medical Center, Los Angeles,  California,  91010,  United States

      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States

      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States

      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States

District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States

Florida
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States

Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States

Illinois
      Children's Memorial Hospital, Chicago, Chicago,  Illinois,  60614,  United States

      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States

Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5265,  United States

Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States

Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231,  United States

Massachusetts
      Boston Floating Hospital Infants and Children, Boston,  Massachusetts,  02111,  United States

      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States

Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States

      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States

      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States

Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States

Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States

      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States

      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States

New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08901,  United States

      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States

New York
      Columbia Presbyterian Hospital, New York,  New York,  10032,  United States

      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States

      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States

      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

      Graham Children's Health Center, Asheville,  North Carolina,  28801,  United States

Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States

      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States

Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73190,  United States

Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States

      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States

South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States

Tennessee
      Vanderbilt Cancer Center, Nashville,  Tennessee,  37232-6838,  United States

Texas
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States

      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  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

Utah
      Primary Children's Medical Center, Salt Lake City,  Utah,  84113,  United States

Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States

Wisconsin
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States

      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Australia, Victoria
      Royal Children's Hospital, Parkville,  Victoria,  3052,  Australia

Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia

Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada

Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada

      Montreal Children's Hospital, Montreal,  Quebec,  H3H 1P3,  Canada

Study chairs or principal investigators

Denise Adams,  Study Chair,  Pediatric Oncology Group   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000066891; POG-9870
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003765
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005