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Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00363272
First received: August 10, 2006
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

This phase I trial is studying the side effects and best dose of ispinesib in treating young patients with relapsed or refractory solid tumors or lymphoma. Drugs used in chemotherapy, such as ispinesib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing


Condition Intervention Phase
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
Drug: ispinesib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE 1 STUDY OF ISPINESIB (SB-715992) IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID TUMORS

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: June 2006
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: ispinesib
Given IV
Other Names:
  • CK0238273
  • SB-715992
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00363272

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Sills Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00363272     History of Changes
Other Study ID Numbers: NCI-2012-01828, ADVL0517, U01CA097452, CDR0000491407
Study First Received: August 10, 2006
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adamantinoma
Astrocytoma
Brain Neoplasms
Burkitt Lymphoma
Choroid Plexus Neoplasms
Craniopharyngioma
Ependymoma
Glioma
Lymphoma
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Medulloblastoma
Meningioma
Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Optic Nerve Glioma
Spinal Cord Neoplasms
Bone Diseases
Bone Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Cerebral Ventricle Neoplasms
Cranial Nerve Diseases
Cranial Nerve Neoplasms
DNA Virus Infections
Epstein-Barr Virus Infections
Eye Diseases

ClinicalTrials.gov processed this record on November 25, 2014