Irinotecan in Treating Children With Refractory Solid Tumors

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00004078

Collaborator

National Cancer Institute (NCI) (NIH)

181

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Central Nervous System Germ Cell Tumor Childhood Choroid Plexus Tumor Childhood Craniopharyngioma Childhood Grade I Meningioma Childhood Grade II Meningioma Childhood Grade III Meningioma Childhood Infratentorial Ependymoma Childhood Oligodendroglioma Childhood Supratentorial Ependymoma Previously Treated Childhood Rhabdomyosarcoma Recurrent Childhood Cerebellar Astrocytoma Recurrent Childhood Cerebral Astrocytoma Recurrent Childhood Ependymoma Recurrent Childhood Medulloblastoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Visual Pathway and Hypothalamic Glioma Recurrent Childhood Visual Pathway Glioma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Neuroblastoma Recurrent Osteosarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Drug: irinotecan hydrochloride	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

181 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Irinotecan in Children With Refractory Solid Tumors

Study Start Date :

Oct 1, 1999

Actual Primary Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (irinotecan hydrochloride) 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.	Drug: irinotecan hydrochloride Given IV Other Names: Campto Camptosar CPT-11 irinotecan U-101440E

Arm

Intervention/Treatment

Experimental: Treatment (irinotecan hydrochloride)

Drug: irinotecan hydrochloride

Given IV

Other Names:

Campto

Camptosar

CPT-11

irinotecan

U-101440E

Outcome Measures

Primary Outcome Measures

Objective response (PR or CR), recorded according to standard solid tumor response criteria [Up to 8 years]

Secondary Outcome Measures

Toxicity, graded using the NCI CTCAE version 2.0 [Up to 8 years]
Pharmacokinetics of irinotecan hydrochloride [Day 1 of course 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)