Clinical trial NCT00004078: Irinotecan in Treating Children With Refractory Solid Tumors
Official title: Phase II Trial of Irinotecan in Children With Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-28
Enrollment: 181
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Objective response (PR or CR), recorded according to standard solid tumor response criteria
timeFrame: Up to 8 years
Secondary outcomes:
measure: Toxicity, graded using the NCI CTCAE version 2.0
timeFrame: Up to 8 years
measure: Pharmacokinetics of irinotecan hydrochloride
timeFrame: Day 1 of course 1
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Lisa Bomgaars
role: PRINCIPAL_INVESTIGATOR
References: