Phase II Trial of Irinotecan in Children With Refractory Solid Tumors
1 Year
21 Years
Both
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
Trial Information
Phase II Trial of Irinotecan in Children With Refractory Solid Tumors
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.
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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective response (PR or CR), recorded according to standard solid tumor response criteria
Outcome Time Frame:
Up to 8 years
Safety Issue:
No
Principal Investigator
Lisa Bomgaars
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
P9761
NCT ID:
NCT00004078
Start Date:
October 1999
Completion Date:
Related Keywords:
- 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
- Astrocytoma
- Craniopharyngioma
- Adamantinoma
- Ependymoma
- Glioma
- Medulloblastoma
- Meningioma
- Neuroblastoma
- Oligodendroglioma
- Osteosarcoma
- Rhabdomyosarcoma
- Choroid Plexus Neoplasms
- Neoplasms, Germ Cell and Embryonal
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Rhabdomyosarcoma, Embryonal
- Optic Nerve Glioma
- Neoplasms
- Sarcoma, Ewing's
- Neuroectodermal Tumors, Primitive, Peripheral
- Sarcoma
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
