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Irinotecan in Treating Children With Refractory Solid Tumors

This study has been completed.
Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  Irinotecan in Treating Children With Refractory Solid Tumors
Official Title  Phase II Trial of Irinotecan in Children With Refractory Solid Tumors
Brief Summary

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

PURPOSE: This phase II trial is studying irinotecan to see how well it works in treating children with refractory solid tumors.

Detailed Description

OBJECTIVES:

  • Determine the efficacy of irinotecan in children with refractory CNS or solid tumors.
  • Assess the toxicity, pharmacokinetics, and pharmacodynamics of this regimen in this patient population.
  • Determine patient UGT1A1 genotype and correlate genotype with toxicity and pharmacokinetic parameters of this regimen in these patients.

OUTLINE: Patients are stratified according to type of solid tumor (Ewings/PNET vs neuroblastoma vs osteosarcoma vs rhabdomyosarcoma vs other solid tumors excluding lymphomas and brain tumors) or brain tumor (medulloblastoma/PNET vs brain stem glioma vs ependymoma vs other CNS tumors).

Patients receive irinotecan IV over 60 minutes on days 1-5. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 4 years and then annually thereafter until death or until patient enters another POG study.

PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study.

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment
Primary Outcome Measure  Efficacy [ Designated as safety issue: No ]
Secondary Outcome Measure  Toxicity [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]
Pharmacodynamics [ Designated as safety issue: No ]
Condition  Brain and Central Nervous System Tumors
Neuroblastoma
Sarcoma
Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  Drug: irinotecan hydrochloride
MEDLINE PMIDs 18278496,   17925558
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Completed
Enrollment  225
Start Date  October 1999
Completion Date
Eligibility Criteria 

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed CNS or solid tumors recurrent or refractory to standard therapy

    • Solid tumors:

      • Neuroblastoma
      • Ewing's Sarcoma/peripheral primitive neuroectodermal tumor (PNET)
      • Osteosarcoma
      • Rhabdomyosarcoma
      • Other extracranial solid tumors
    • CNS tumors:

      • Medulloblastoma/PNET
      • Ependymoma
      • Brain stem glioma
      • Other CNS tumor
      • Intrinsic brain stem tumor (biopsy required only if previously treated with radiosurgery)
      • Classic optic glioma (histologic requirement waived)
  • Measurable disease by imaging studies

    • No lesions assessable only by radionuclide scan
  • Previously irradiated lesions used to evaluate tumor response must show evidence of an interim increase in size

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21

Performance status:

  • Karnofsky 50-100% if more than 10 years old OR
  • Lansky 50-100% if 10 years or younger

Life expectancy:

  • At least 8 weeks

Hematopoietic:

  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 100,000/mm^3
  • Hemoglobin greater than 8 mg/dL
  • Inadequate peripheral blood counts due to bone marrow infiltration allowed

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • SGPT less than 5 times normal

Renal:

  • Creatinine normal
  • Glomerular filtration rate at least 70 mL/min

Other:

  • No severe uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 3 weeks since prior immunotherapy and recovered
  • No concurrent biologic therapy

Chemotherapy:

  • At least 3 weeks since prior chemotherapy (8 weeks since prior nitrosoureas) and recovered
  • No more than 2 prior chemotherapy regimens
  • No other concurrent chemotherapy
  • Prior topotecan allowed
  • No prior irinotecan

Endocrine therapy:

  • Concurrent dexamethasone for brain tumor patients allowed if on a stable or decreasing dose for at least 2 weeks prior to study
  • At least 3 weeks since prior endocrine therapy
  • No other concurrent endocrine therapy

Radiotherapy:

  • See Disease Characteristics
  • At least 8 weeks since prior extended radiotherapy (including evaluable lesions) and recovered
  • No prior total body radiotherapy
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics

Other:

  • At least 3 weeks since prior investigational agents
  • No other concurrent investigational agents
  • No concurrent anticonvulsants
  • No concurrent medications that would interfere with the P-450 enzyme system function (e.g., erythromycin, cimetidine, fluconazole)
Gender Both
Ages 1 Year to 21 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States,   Australia,   Canada,   Puerto Rico,   Switzerland
Administrative Information Fields
NCT ID  NCT00004078
Organization ID CDR0000067288
Secondary IDs †† COG-P9761, POG-9761, CCG-P9761
Study Sponsor  Children's Oncology Group
Collaborators †† National Cancer Institute (NCI)
Investigators 
Study Chair:     Lisa Bomgaars, MD     Texas Children's Cancer Center    
Information Provided By National Cancer Institute (NCI)
Verification Date November 2005
First Received Date  December 10, 1999
Last Updated Date May 23, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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