Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Irinotecan in Treating Children With Refractory Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	1 to 21	NCI	COG-P9761 POG-9761, CCG-P9761, NCT00004078, P9761

Objectives

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

Entry 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

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)

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/mm³
• Platelet count greater than 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Efficacy

Toxicity
Pharmacokinetics
Pharmacodynamics

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.

Thompson PA, Gupta M, Rosner GL, et al.: Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children's oncology group. Cancer Chemother Pharmacol 62 (6): 1027-37, 2008.[PUBMED Abstract]

Bomgaars LR, Bernstein M, Krailo M, et al.: Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol 25 (29): 4622-7, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Lisa Bomgaars, MD, Protocol chair		Ph: 832-824-4588 Email: lbomgaars@txccc.org

Registry Information
Official Title		Phase II Trial of Irinotecan in Children with Refractory Solid Tumors
Trial Start Date		1999-10-01
Registered in ClinicalTrials.gov		NCT00004078
Date Submitted to PDQ		1999-08-27
Information Last Verified		2005-11-17
NCI Grant/Contract Number		CA30969

Back to Top