A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors
filgrastim
+ cyclophosphamide
+ tirapazamine
Treatment Study
Summary
Study start date: August 1, 1998
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.12 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Until 21 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Criteria
DISEASE CHARACTERISTICS: Histologically confirmed solid tumor that is refractory to conventional therapy or for which no effective therapy is known Brain tumors eligible Brainstem gliomas may waive histological verification requirement Neurologic deficits associated with CNS malignancies must be stable for a minimum of 4 weeks prior to study No leukemia Stratum 2 No marrow involvement PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Karnofsky or Lansky 50-100% Life expectancy: At least 8 weeks Absolute neutrophil count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL Bilirubin less than 1.5 mg/dL SGPT less than 5 times normal Creatinine normal for age OR creatinine clearance at least 70 mL/min Shortening fraction at least 27% of normal OR ejection fraction greater than 50% of normal Not pregnant or nursing Negative pregnancy test required PRIOR CONCURRENT THERAPY: No concurrent anticancer therapy At least 6 months since bone marrow transplant and no evidence of graft versus host disease At least 1 week since growth factors No concurrent granulocyte colony-stimulating factor Recovered from prior immunotherapy Stratum 2: No prior bone marrow transplantation (with or without total body irradiation) At least 6 weeks since prior nitrosourea At least 2 weeks since other prior myelosuppressive chemotherapy Dexamethasone must be a stable or decreasing dose for 2 weeks prior to study Recovered from prior chemotherapy Stratum 2: No more than 2 prior chemotherapy regimens At least 2 weeks since local palliative radiotherapy (small port) At least 6 months since prior substantial bone marrow radiation (e.g., cross- sectional radiotherapy [greater than 24 Gy], total body irradiation, hemi- pelvic radiotherapy) Recovered from prior radiotherapy Stratum 2: No prior central axis radiation
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 28 locations
University of Alabama Comprehensive Cancer Center
Birmingham, United StatesOpen University of Alabama Comprehensive Cancer Center in Google MapsUniversity of Arkansas for Medical Sciences
Little Rock, United StatesUniversity of California San Diego Cancer Center
La Jolla, United StatesLucile Packard Children's Hospital at Stanford
Palo Alto, United States