Clinical trial NCT00003370: Irofulven in Treating Children With Recurrent or Refractory Solid Tumors
Official title: A Trial of MGI 114 in Children With Solid Tumors: A Pediatric Oncology Group Phase I Cooperative Agreement Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: unspecified childhood solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-02-09
Enrollment: 12
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital, Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Boston Floating Hospital Infants and Children
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Huntington
country: United States
facility: Veterans Affairs Medical Center - Huntington
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center - Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: University of Mississippi Cancer Clinic
name: Gail C. Megason, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1002/pbc.20686.