Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Carboplatin and Irinotecan in Treating Children With Refractory Solid Tumors

Summary: 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.

Detailed description: 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.

Eligibility: 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)

Relevance to patient case: not relevant