Irinotecan in Treating Children With Refractory Solid Tumors

Phase II Trial of Irinotecan in Children With Refractory Solid Tumors

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.

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: irinotecan; Campto; Camptosar; U-101440E; CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response (PR or CR), recorded according to standard solid tumor response criteria	Up to 8 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity, graded using the NCI CTCAE version 2.0	Up to 8 years
Pharmacokinetics of irinotecan hydrochloride	Day 1 of course 1

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lisa Bomgaars, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: October 1, 1999
• Primary Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Estimate): June 14, 2013
• Last Update Submitted That Met QC Criteria: June 13, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Musculoskeletal Diseases; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Bone Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Neoplasms, Vascular Tissue; Neoplasms, Muscle Tissue; Meningeal Neoplasms; Myosarcoma; Bone Neoplasms; Cerebral Ventricle Neoplasms; Neoplasms; Recurrence; Glioma; Sarcoma, Ewing; Ependymoma; Medulloblastoma; Osteosarcoma; Astrocytoma; Oligodendroglioma; Neuroblastoma; Meningioma; Rhabdomyosarcoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Rhabdomyosarcoma, Embryonal; Craniopharyngioma; Adamantinoma; Choroid Plexus Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: P9761; U10CA098543 (U.S. NIH Grant/Contract); NCI-2012-02310 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000067288 (Other Identifier: Clinical Trials.gov); POG-9761 (Other Identifier: Pediatric Oncology Group); CCG-P9761 (Other Identifier: Children's Cancer Group); COG-P9761 (Other Identifier: Children's Oncology Group)