Irinotecan and Cisplatin With or Without Amifostine in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy
Condition: Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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. 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.
    

Detailed description: 
      PRIMARY 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.

      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.
    

Intervention name(s): cisplatin; irinotecan hydrochloride; amifostine trihydrate; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): Given IV; Given IV; Given IV; Correlative studies
Other intervention name(s): CACP; CDDP; CPDD; DDP; Campto; Camptosar; CPT-11; irinotecan; U-101440E; ethiofos; Ethyol; gammaphos; WR-2721; pharmacological studies
Intervention MeSH terms: Irinotecan; Amifostine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment