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

January 15, 2013 updated by: National Cancer Institute (NCI)

A PHASE 1 STUDY OF ISPINESIB (SB-715992) IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID TUMORS

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: ispinesib
Given IV
Other Names:
  • CK0238273
  • SB-715992

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Up to 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Richard Sills, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

August 10, 2006

First Submitted That Met QC Criteria

August 10, 2006

First Posted (Estimate)

August 15, 2006

Study Record Updates

Last Update Posted (Estimate)

January 16, 2013

Last Update Submitted That Met QC Criteria

January 15, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01828
  • U01CA097452 (U.S. NIH Grant/Contract)
  • ADVL0517
  • CDR0000491407 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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