Irinotecan in Treating Children With Refractory Solid Tumors

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Recurrent Childhood Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Childhood Supratentorial Ependymoma; Childhood Central Nervous System Germ Cell Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Childhood Infratentorial Ependymoma; Childhood Grade III Meningioma; Recurrent Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Craniopharyngioma; Childhood Grade II Meningioma; Previously Treated Childhood Rhabdomyosarcoma; Childhood Choroid Plexus Tumor; Unspecified Childhood Solid Tumor, Protocol Specific; Childhood Oligodendroglioma; Recurrent Childhood Rhabdomyosarcoma

Treatments: Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00004078

CCG-P9761 (Other Identifier)

P9761

NCI-2012-02310 (Registry Identifier)

CDR0000067288 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

POG-9761 (Other Identifier)

COG-P9761 (Other Identifier)

Details and patient eligibility

About

This phase II trial is studying irinotecan to see how well it works in treating children with refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Full description

OBJECTIVES:

I. Determine the efficacy of irinotecan in children with refractory CNS or solid tumors.

II. Assess the toxicity, pharmacokinetics, and pharmacodynamics of this regimen in this patient population.

III. 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.

Enrollment: 181 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• 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

• Performance status - Karnofsky 50-100% if more than 10 years old

• Performance status - Lansky 50-100% if 10 years or younger

• At least 8 weeks

• 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

• Bilirubin no greater than 1.5 mg/dL

• SGPT less than 5 times normal

• Creatinine normal

• Glomerular filtration rate at least 70 mL/min

• No severe uncontrolled infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after study

• At least 3 weeks since prior immunotherapy and recovered

• No concurrent biologic therapy

• 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

• 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

• See Disease Characteristics

• At least 8 weeks since prior extended radiotherapy (including evaluable lesions) and recovered

• No prior total body radiotherapy

• No concurrent radiotherapy

• See Disease Characteristics

• 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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181 participants in 1 patient group

Treatment (irinotecan hydrochloride)

Experimental group

Description:

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.

Treatment:

Drug: irinotecan hydrochloride