RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase I trial to study the effectiveness of irinotecan and cisplatin with or without amifostine in treating children who have solid tumors that have not responded to previous therapy.

Condition	Treatment or Intervention	Phase
unspecified childhood solid tumor, protocol specific Drug Toxicity	Procedure: chemotherapy  Behavior: supportive care/therapy  Drug: chemoprotection  Drug: amifostine  Drug: cisplatin  Drug: irinotecan	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of irinotecan when administered with cisplatin, with or without amifostine, to children with refractory solid tumors. II. Determine the dose limiting toxicities of the combination of irinotecan and cisplatin, with and without amifostine, in this patient population. III. Determine the pharmacokinetics of cisplatin with and without amifostine in these patients. IV. Quantify the leukocyte DNA-platinum adduct formation, with and without amifostine, and correlate it with response and toxicity in these patients. V. Determine the safety and efficacy of the doses and schedules of administration to be used in phase II clinical trials.

PROTOCOL OUTLINE: This is a dose escalation study of irinotecan. Treatment A: Patients receive cisplatin IV over 1 hour followed immediately by irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 6 weeks. Treatment continues for a minimum of 2 courses in the absence of unacceptable toxicity or disease progression. Treatment B: Patients receive therapy as in treatment A. In addition, amifostine IV is administered over 15 minutes immediately before cisplatin. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Once the MTD of treatment A is determined, additional patients are accrued to determine the MTD of treatment B. If myelosuppression is the dose limiting toxicity of treatment A, then stratum 1 closes and stratum 2 opens and these patients with less prior therapy receive treatment A. Treatment B is then only open to stratum 3 patients. Patients are followed every 6 months for 4 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2.5 years.

Ages Eligible for Study:  1 Year   -   21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed solid tumor that is refractory to standard therapy or for which no effective therapy exists; Brainstem gliomas allowed without histologic diagnosis; Brain tumors allowed provided not receiving anticonvulsants
• Strata 2 and 3: No bone marrow involvement

--Prior/Concurrent Therapy--

• Biologic therapy: At least 1 week since prior biologic therapy and recovered; At least 6 months since prior autologous or allogeneic bone marrow transplantation without total body irradiation (TBI); At least 1 week since prior growth factors; Strata 2 and 3: No prior stem cell transplantation (with or without TBI)
• Chemotherapy: At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered; At least 1 week since prior antineoplastic agents; No other concurrent chemotherapy; Strata 2 and 3: No more than 2 prior chemotherapy regimens (single or multiagent)
• Endocrine therapy: If receiving dexamethasone for CNS tumors, must be on stable or decreasing dose for at least 2 weeks
• Radiotherapy: At least 2 weeks since prior local radiation (small port); At least 6 months since prior craniospinal radiation; At least 6 months since prior radiation to at least 50% of pelvis; At least 6 weeks since prior substantial bone marrow radiation; Recovered from prior radiotherapy; Strata 2 and 3: No prior central axis radiotherapy
• Surgery: Not specified
• Other: No other concurrent investigational agents; No other concurrent anticancer therapy; No concurrent anticonvulsants

--Patient Characteristics--

• Age: 1 to 21
• Performance status: Karnofsky 50-100% for patients over 10 years of age OR Lansky 50-100% for patients 10 years of age and under
• Life expectancy: At least 8 weeks
• Hematopoietic: Absolute neutrophil count at least 1,000/mm3; Hemoglobin at least 8.0 g/dL; Platelet count at least 100,000/mm3
• Hepatic: Albumin at least 2.5 g/dL; Bilirubin no greater than 1.5 mg/dL; SGPT no greater than 2 times upper limit of normal
• Renal: Creatinine normal for age OR GFR normal for age
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; If CNS tumor, neurologic deficits relatively stable for at least 2 weeks; Must be at least third percentile weight for height; No concurrent significant systemic illness (e.g., infection, fever, mucositis, severe anorexia, and severe malnutrition); No uncontrolled infections; No evidence of graft versus host disease

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, Duarte,  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,  94143-0128,  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,  60611-3013,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  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
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-Ingram 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,  53792-6164,  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
      McGill University Health Center - Montreal Children's Hospital, Montreal,  Quebec,  H3H 1P3,  Canada

Study chairs or principal investigators

Abdul Kader Souid,  Study Chair,  Pediatric Oncology Group   

Study ID Numbers:  CDR0000067601; POG-9970; CCG-P9970
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004919
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08