Irofulven in Treating Children With Recurrent or Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003370
First received: November 1, 1999
Last updated: February 4, 2013
Last verified: May 2006
  Purpose

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.


Condition Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: irofulven
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of MGI 114 in Children With Solid Tumors: A Pediatric Oncology Group Phase I Cooperative Agreement Study

Resource links provided by NLM:


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

Enrollment: 12
Study Start Date: August 1998
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: irofulven

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.

  Eligibility

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

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
  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: NCT00003370

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

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003370     History of Changes
Other Study ID Numbers: NCI-2012-01838, POG-9772, CDR0000066359
Study First Received: November 1, 1999
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Irofulven
Radiation-Sensitizing Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 18, 2014