A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors
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.
Interventional
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Victor Aquino, MD
Study Chair
Simmons Cancer Center
United States: Food and Drug Administration
NCI-2012-01837
NCT00003288
August 1998
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
University of Alabama Comprehensive Cancer Center | Birmingham, Alabama 35294 |
Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
Johns Hopkins Oncology Center | Baltimore, Maryland 21287 |
University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
Simmons Cancer Center - Dallas | Dallas, Texas 75235-9154 |
Sylvester Cancer Center, University of Miami | Miami, Florida 33136 |
Children's Hospital of Michigan | Detroit, Michigan 48201 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
University of California San Diego Cancer Center | La Jolla, California 92093-0658 |
State University of New York - Upstate Medical University | Syracuse, New York 13210 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
Hackensack University Medical Center | Hackensack, New Jersey 07601 |
Floating Hospital for Children | Boston, Massachusetts 02111 |
Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
Lucile Packard Children's Hospital at Stanford | Palo Alto, California 94304 |
Saint Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
Children's Memorial Hospital, Chicago | Chicago, Illinois 60614 |