RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of combining carboplatin and irinotecan in treating children who have refractory solid tumors.

Condition	Treatment or Intervention	Phase
unspecified childhood solid tumor, protocol specific	Drug: carboplatin  Drug: irinotecan  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of carboplatin and irinotecan in children with refractory solid tumors.
• Determine the safety profile and dose-limiting toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the preliminary anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of carboplatin and irinotecan.

Patients receive carboplatin IV over 50 minutes on day 1 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for at least 30 days.

PROJECTED ACCRUAL: A total of 25-30 patients will be accrued for this study within 6-9 months.

Ages Eligible for Study:  1 Year   -   21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor, including primary brain tumor
• Progressive disease on standard therapy or for which no standard therapy exists
• No symptomatic brain metastases

PATIENT CHARACTERISTICS: Age:

• 1 to 21

Performance status:

• Lansky 50-100% (age 10 and under)
• Karnofsky 50-100% (over age 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT no greater than 2.5 times upper limit of normal

Renal:

• Glomerular filtration rate at least 30 mL/min

Other:

• No active infection
• No serious uncontrolled medical disorder
• No psychiatric disorder or other disorder that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 6 months since prior allogeneic bone marrow transplantation without evidence of acute or chronic graft versus host disease
• At least 3 months since prior autologous bone marrow or peripheral blood stem cell transplantation
• At least 4 weeks since prior immunotherapy and recovered
• No concurrent immunotherapy

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent hormone replacement therapy or oral contraceptives allowed
• No other concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy (including for brain metastases) and recovered
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational anticancer drugs
• No other concurrent antitumor therapy
• No concurrent anticonvulsants (e.g., phenytoin, phenobarbital, or carbamazepine) except gabapentin (Neurontin)

Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2916,  United States
Missouri
      Washington University Medical Center, Saint Louis,  Missouri,  63105,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
Pennsylvania
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada

Study chairs or principal investigators

Ashwin Gollerkeri, MD,  Study Chair,  Bristol-Myers Squibb   

Study ID Numbers:  CDR0000068908; BMS-CA124-001; CNMC-2782; MSKCC-01071; SJCRH-CARCPT; NCI-G01-2016
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024284
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08