ABT-751 in Treating Young Patients With Refractory Solid Tumors

March 14, 2012 updated by: National Institutes of Health Clinical Center (CC)

Phase I Trial and Pharmacokinetic Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients With Refractory Solid Tumors

RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects of ABT-751 in treating young patients with refractory solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and dose-limiting toxic effects of ABT-751 administered daily for 7 days every 21 days or daily for 21 days every 28 days in children with refractory solid tumors.
  • Determine the toxicity spectrum of these regimens in these patients.
  • Determine the pharmacokinetics of these regimens in these patients.
  • Evaluate the pharmacodynamics of this drug by measuring the fraction of tubulin that is polymerized in the peripheral blood mononuclear cells of these patients before and after receiving this drug.

Secondary

  • Quantify responses in patients treated with these regimens.
  • Assess the effect of this drug on tumor vascularity and tumor blood flow using dynamic enhanced MRI in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of 2 different schedules of ABT-751. Patients are assigned to 1 of 2 dosing schedules.

  • Schedule 1 (closed to accrual as of 5/25/2009): Patients receive oral ABT-751 once daily on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Schedule 2 (closed to accrual as of 5/25/2009): Patients receive oral ABT-751 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

On each schedule, cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 9 patients (a minimum of 3 patients age 11 and under and 3 patients age 12 to 18) are treated at the MTD.

PROJECTED ACCRUAL: A maximum of 90 patients will be accrued for this study within 8 months.

Study Type

Interventional

Enrollment (Anticipated)

90

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
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4318
        • Children's Hospital of Philadelphia

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

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor*, including, but not limited to, the following:

    • Rhabdomyosarcoma
    • Other soft tissue sarcomas
    • Ewing's sarcoma family of tumors
    • Osteosarcoma
    • Neuroblastoma
    • Wilms' tumor
    • Hepatic tumors
    • Germ cell tumors
    • Primary brain tumors
    • Brain stem or optic gliomas (histological confirmation may be waived if a biopsy has not been performed) NOTE: *Closed to accrual for all diagnoses except neuroblastoma as of 4/16/05
  • Relapsed after or failed to respond to frontline standard therapy and no other standard treatment options (e.g., surgery, radiotherapy, chemotherapy, or any combination of these modalities) exist
  • Measurable or evaluable disease* NOTE: *Not required for patients with neuroblastoma
  • No CNS tumor with motor or sensory deficits that would obscure the study assessment of sensory neuropathy

PATIENT CHARACTERISTICS:

Age:

  • 18 and under

Performance status:

  • Lansky 60-100% (age 10 and under)
  • Karnofsky 60-100% (age 11 to 18)

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • ALT and AST no greater than 2.5 times ULN (5 times ULN for patients treated after the maximum tolerated dose is determined)
  • No clinically significant hepatic dysfunction

Renal:

  • Creatinine normal for age OR
  • Creatinine clearance at least 60 mL/min
  • No clinically significant renal dysfunction

Cardiovascular:

  • LVEF normal by echocardiogram

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No allergy to sulfa-containing medications
  • No clinically significant unrelated systemic illness (e.g., other organ dysfunction) that would preclude study participation
  • No serious infection
  • No preexisting grade 2 or greater sensory or motor neuropathy
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 months since prior bone marrow transplantation
  • At least 72 hours since prior interleukin-11
  • At least 72 hours since prior colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa

  • No concurrent growth factors (e.g., GM-CSF) except epoetin alfa

    • Concurrent G-CSF allowed if neutropenia lasts longer than 5 days OR if the patient experiences confirmed septicemia associated with neutropenia
  • No concurrent immunotherapy
  • No concurrent interleukin-11

Chemotherapy:

  • See Disease Characteristics
  • At least 30 days since prior chemotherapy (42 days for nitrosoureas)
  • No other concurrent anticancer chemotherapy

Endocrine therapy:

  • Patients with brain tumors:

    • Must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan performed for the purpose of assessing response to study therapy
    • Concurrent corticosteroids allowed for control of symptoms of tumor-associated edema

Radiotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • At least 4 months since prior extensive radiotherapy (craniospinal radiotherapy, total body irradiation, or radiotherapy to more than 50% of the pelvis)
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics

Other:

  • Recovered from prior therapy
  • At least 30 days since prior investigational anticancer therapy
  • No other concurrent investigational agents

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
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Elizabeth Fox, MD, National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2002

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

May 13, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

March 15, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020141
  • 02-C-0141
  • ABBOTT-M01-357
  • CDR0000069344

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.

Clinical Trials on Sarcoma

Clinical Trials on ABT-751

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Algeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe