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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
History of Changes
  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:

MedlinePlus related topics: Cancer
U.S. FDA Resources

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003370

  Show 56 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Study Chair: Gail C. Megason, MD University of Mississippi Cancer Clinic
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

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
Physiological Effects of Drugs
Pharmacologic Actions
 Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013