Irofulven in Treating Children With Recurrent or Refractory Solid Tumors

February 4, 2013 updated by: National Cancer Institute (NCI)

A Trial of MGI 114 in Children With Solid Tumors: A Pediatric Oncology Group Phase I Cooperative Agreement Study

Phase I trial to study the effectiveness of irofulven in treating children with recurrent or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells so they stop growing or die.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose and dose limiting toxicity of 6-hydroxymethylacylfulvene (MGI-114) in pediatric patients with recurrent or refractory solid tumors.

II. Determine the incidence and severity of other toxic effects of MGI-114. III. Determine a safe and tolerable dose of MGI-114 to be used in phase II studies.

IV. Determine the pharmacokinetics of MGI-114 in these patients. V. Determine preliminary evidence of antitumor activity of MGI-114 against recurrent or refractory pediatric solid tumors.

OUTLINE: This is a dose escalation study. If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens.

Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.

Study Type

Interventional

Enrollment (Actual)

12

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

    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
      • Montreal, Quebec, Canada, H3H 1P3
        • McGill University Health Center - Montreal Children's Hospital
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • La Jolla, California, United States, 92093-0658
        • University of California San Diego Cancer Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94143-0128
        • UCSF Cancer Center and Cancer Research Institute
      • Stanford, California, United States, 94305-5408
        • Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital, Chicago
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Boston Floating Hospital Infants and Children
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0752
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Columbia Presbyterian Hospital
      • Syracuse, New York, United States, 13210
        • State University of New York - Upstate Medical University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Children's Hospital Medical Center - Cincinnati
      • Columbus, Ohio, United States, 43205-2696
        • Children's Hospital of Columbus
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73190
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75235-9154
        • Simmons Cancer Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center
      • San Antonio, Texas, United States, 78284-7811
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • West Virginia
      • Huntington, West Virginia, United States, 25704
        • Veterans Affairs Medical Center - Huntington
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

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 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven recurrent or refractory solid tumors
  • No leukemia
  • Patients with brain tumors are not eligible until the first 2 patients at each dose level are evaluable for toxicity

PATIENT CHARACTERISTICS:

  • Age: 21 and under
  • Performance status: Karnofsky 50-100% Lansky play scale 50-100% (for infants)
  • Life expectancy: At least 8 weeks
  • Absolute neutrophil count at least 1,000/mm3
  • Hemoglobin at least 9 g/dL
  • Platelet count at least 75,000/mm3
  • Bilirubin less than 1.5 mg/dL
  • SGPT less than 5 times upper limit of normal
  • Creatinine normal for age OR GFR at least 70 mL/min
  • Cardiac shortening fraction at least 27% OR institutional normal OR cardiac ejection fraction greater than 50% OR institutional normal
  • Neurologic deficits in patients with CNS tumors must be stable for at least 2 weeks
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after the study
  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:

  • At least 1 week since prior growth factor therapy and recovered
  • At least 6 months since prior bone marrow transplantation and no evidence of graft versus host disease
  • At least 2 weeks since prior myelosuppressive chemotherapy and recovered
  • At least 6 weeks since prior nitrosourea and recovered
  • At least 2 weeks on stable dexamethasone for patients with CNS tumors
  • No concurrent chemotherapy
  • At least 2 weeks since prior palliative radiotherapy (small port)
  • At least 6 months since prior substantial bone marrow radiation
  • At least 6 months since total abdominal, pelvic, chest, mantle, and Y ports radiotherapy
  • No other concurrent anticancer therapy or 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
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I

If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens.

Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.

Collaborators and Investigators

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

Investigators

  • Study Chair: Gail C. Megason, MD, University of Mississippi Cancer Clinic

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.

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

August 1, 1998

Primary Completion (Actual)

March 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

February 6, 2004

First Posted (Estimate)

February 9, 2004

Study Record Updates

Last Update Posted (Estimate)

February 5, 2013

Last Update Submitted That Met QC Criteria

February 4, 2013

Last Verified

May 1, 2006

More Information

Terms related to this study

Other Study ID Numbers

  • NCI-2012-01838
  • POG-9772
  • CDR0000066359 (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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