A PHASE 1 STUDY OF ISPINESIB (SB-715992) IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID TUMORS
1 Year
21 Years
Both
Childhood Burkitt Lymphoma, 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 High-grade Cerebral Astrocytoma, Childhood Infratentorial Ependymoma, Childhood Low-grade Cerebral Astrocytoma, Childhood Spinal Cord Neoplasm, Childhood Supratentorial Ependymoma, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway and Hypothalamic Glioma, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A PHASE 1 STUDY OF ISPINESIB (SB-715992) IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID TUMORS
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of ispinesib in
pediatric patients with refractory solid tumors or lymphoma.
II. Define and describe the toxicities of ispinesib in these patients. III. Characterize the
pharmacokinetics of ispinesib in these patients.
SECONDARY OBJECTIVES:
I. Define, preliminarily, the antitumor activity of ispinesib. II. Determine the
relationship between CYP3A4 gene polymorphisms and pharmacokinetics in patients treated with
this regimen.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive ispinesib IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28
days for 24 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ispinesib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Patients undergo blood and tumor sample collection periodically for pharmacokinetic and gene
polymorphism correlative studies.
After completion of study therapy, patients are followed for 30 days.
Inclusion Criteria:
- Histologically confirmed malignancy at either original diagnosis or relapse,
including the following:
- Solid tumor, including primary CNS tumors
- Neurologic deficits in patients with CNS tumors must have been relatively
stable for ≥ 1 week
- Patients with CNS tumors must be on stable or decreasing doses of
dexamethasone for the past 7 days
- Histology requirement waived for intrinsic brain stem tumors
- Lymphoma
- Measurable or evaluable disease
- No known curative therapy or no therapy proven to prolong survival with an acceptable
quality of life exists
- Patients with known bone marrow metastases are eligible for study but are not
evaluable for hematologic toxicity
- Not known to be refractory to red blood cell or platelet transfusions
- Karnofsky performance score (PS) 60-100% (> 10 years of age) or Lansky PS 60-100% (≤
10 years of age)
- Absolute neutrophil count ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³ (transfusion independent, defined as not receiving
platelet transfusions within a 7-day period prior to study enrollment)
- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
creatinine based on age as follows:
- No greater than 0.8 mg/dL (≤ 5 years of age)
- No greater than 1.0 mg/dL (6 to 10 years of age)
- No greater than 1.2 mg/dL (11 to 15 years of age)
- No greater than 1.5 mg/dL (> 15 years of age)
- Bilirubin ≤ 1.5 times upper limit of normal
- ALT ≤ 45 U/L
- Albumin ≥ 2 g/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of active graft-vs-host disease
- No uncontrolled infection
- Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or
radiotherapy
- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas)
- More than 1 week since prior growth factors, including those that support platelet or
WBC number or function
- At least 1 week since prior biologic agents
- At least 2 weeks since prior local, palliative, small-port external-beam
radiotherapy
- At least 6 months since prior total body irradiation (TBI), craniospinal
radiotherapy, or radiotherapy to ≥ 50%of the pelvis
- At least 6 weeks since other prior substantial bone marrow radiotherapy (i.e., skull,
spine, pelvis, or ribs)
- At least 3 months since prior stem cell transplantation or rescue without TBI
- No other concurrent investigational drugs
- No other concurrent anticancer agents, including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy
- No concurrent enzyme-inducing anticonvulsants, including any of the following:
- Phenytoin
- Phenobarbital
- Felbamate
- Primdone
- Oxcarbazepine
- Carbamazepine
- No concurrent agents that inhibit CYP3A4, including any of the following:
- Itraconazole
- Ketoconazole
- Voriconazole
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose, defined as the maximum dose at which fewer than one-third of patients experience DLT, graded according to NCI CTCAE version 3.0
Outcome Time Frame:
Up to 28 days
Safety Issue:
Yes
Principal Investigator
Richard Sills
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01828
NCT ID:
NCT00363272
Start Date:
June 2006
Completion Date:
Related Keywords:
- Childhood Burkitt Lymphoma
- 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 High-grade Cerebral Astrocytoma
- Childhood Infratentorial Ependymoma
- Childhood Low-grade Cerebral Astrocytoma
- Childhood Spinal Cord Neoplasm
- Childhood Supratentorial Ependymoma
- Recurrent Childhood Brain Stem Glioma
- Recurrent Childhood Brain Tumor
- Recurrent Childhood Cerebellar Astrocytoma
- Recurrent Childhood Cerebral Astrocytoma
- Recurrent Childhood Ependymoma
- Recurrent Childhood Grade III Lymphomatoid Granulomatosis
- Recurrent Childhood Large Cell Lymphoma
- Recurrent Childhood Lymphoblastic Lymphoma
- Recurrent Childhood Medulloblastoma
- Recurrent Childhood Small Noncleaved Cell Lymphoma
- Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
- Recurrent Childhood Visual Pathway and Hypothalamic Glioma
- Unspecified Childhood Solid Tumor, Protocol Specific
- Astrocytoma
- Brain Neoplasms
- Burkitt Lymphoma
- Neoplasms
- Craniopharyngioma
- Adamantinoma
- Ependymoma
- Glioma
- Lymphoma
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Lymphomatoid Granulomatosis
- Medulloblastoma
- Meningioma
- Spinal Cord Neoplasms
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Choroid Plexus Neoplasms
- Neoplasms, Germ Cell and Embryonal
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Optic Nerve Glioma
- Lymphoma, Extranodal NK-T-Cell
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
