Irofulven in Treating Children With Recurrent or Refractory Solid Tumors

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003370
• Other study ID #: NCI-2012-01838
• Secondary ID: POG-9772CDR00000
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: February 4, 2013
• Start date: August 1998

Study information

• Verified date: May 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• irofulven

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Health Science Center	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Veterans Affairs Medical Center - Huntington	Huntington	West Virginia
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego Cancer Center	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia Presbyterian Hospital	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (1)

Bomgaars LR, Megason GC, Pullen J, Langevin AM, Dale Weitman S, Hershon L, Kuhn JG, Bernstein M, Blaney SM. Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors. Pediatr Blood Cancer. 2006 Aug;47(2):163-8. — View Citation