Tirapazamine Plus Cyclophosphamide in Treating Children With Refractory Solid Tumors
- Conditions
- Unspecified Childhood Solid Tumor, Protocol Specific
- Interventions
- Registration Number
- NCT00003288
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Phase I trial to study the effectiveness of tirapazamine plus cyclophosphamide in treating children who have refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
- Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose and the dose limiting toxicity of tirapazamine when administered with cyclophosphamide as intravenous infusions to children with refractory solid tumors.
II. Determine the incidence and severity of other toxicities of tirapazamine and cyclophosphamide in these patients.
III. Determine a safe and tolerable dose of tirapazamine administered with cyclophosphamide for a phase II study for the same indications.
IV. Determine the pharmacokinetics of tirapazamine in children and adolescents receiving the combination of tirapazamine and cyclophosphamide.
V. Determine the preliminary evidence of antitumor activity of tirapazamine and cyclophosphamide.
OUTLINE: This is a dose escalation study.
Patients receive tirapazamine by 2 hour intravenous infusion (hours 0-2) followed 2 hours later by a 30 minute intravenous infusion of cyclophosphamide. This course is repeated every 3 weeks in patients with partial/complete response or stable disease for a maximum of 1 year. Cohorts of 3-6 patients each are treated at each dose level of tirapazamine. Dose escalation of tirapazamine occurs when 0 of 3 patients or 1 of 6 patients has experienced dose limiting toxicity (DLT). If DLT is experienced in 1 of 3 patients at a given dose level, up to 3 additional patients are treated at that same dose level. If none of the 3 additional patients at that dose level experiences DLT, the dose is escalated. If DLT is experienced in 1 or more of the additional 3 patients, the maximum tolerated dose (MTD) has been exceeded and 3 patients are treated at the next lower dose level (defined as the MTD). A total of six patients are treated at the MTD. If DLT is proved to be neutropenia, patients must then also meet the additional eligibility criteria listed for stratum 2. If neutropenia continues to be the DLT in stratum 2, then additional patients receive subcutaneous filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning 24 hours after cyclophosphamide. A second MTD may be determined for chemotherapy with G-CSF. Patients are followed every 6 months for 4 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I filgrastim See arm description. Arm I cyclophosphamide See arm description. Arm I tirapazamine See arm description.
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (28)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Memorial Hospital, Chicago
🇺🇸Chicago, Illinois, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
University of Alabama Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Sylvester Cancer Center, University of Miami
🇺🇸Miami, Florida, United States
Floating Hospital for Children
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
Lucile Packard Children's Hospital at Stanford
🇺🇸Palo Alto, California, United States
Johns Hopkins Oncology Center
🇺🇸Baltimore, Maryland, United States
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Saint Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
State University of New York - Upstate Medical University
🇺🇸Syracuse, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Simmons Cancer Center - Dallas
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States