|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||
| Sponsors and Collaborators: |
Pediatric Oncology Group National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00003288 |
Purpose
RATIONALE: 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.
PURPOSE: Phase I trial to study the effectiveness of tirapazamine plus cyclophosphamide in treating children who have refractory solid tumors.
| Condition | Intervention | Phase |
|---|---|---|
|
Unspecified Childhood Solid Tumor, Protocol Specific |
Drug: cyclophosphamide Drug: filgrastim Drug: tirapazamine |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors |
| Estimated Enrollment: | 12 |
| Study Start Date: | August 1998 |
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.
PROJECTED ACCRUAL: It is projected that 12 patients will be accrued per year into this study.
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin less than 1.5 mg/dL SGPT less than 5 times normal Renal: Creatinine normal for age OR Creatinine clearance at least 70 mL/min Cardiovascular: Shortening fraction at least 27% of normal OR Ejection fraction greater than 50% of normal Other: Not pregnant or nursing Negative pregnancy test required
PRIOR CONCURRENT THERAPY: No concurrent anticancer therapy Biologic 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) Chemotherapy: 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 Endocrine therapy: Not specified Radiotherapy: 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 Surgery: Not specified
Contacts and Locations
Show 28 Study Locations| Study Chair: | Victor Aquino, MD | Simmons Cancer Center |
More Information
| Study ID Numbers: | CDR0000066219, POG-9675 |
| Study First Received: | November 1, 1999 |
| Last Updated: | July 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00003288 |
| Health Authority: | United States: Federal Government |
|
unspecified childhood solid tumor, protocol specific |
|
Tirapazamine Cyclophosphamide |
|
Radiation-Sensitizing Agents Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Therapeutic Uses Physiological Effects of Drugs |
Myeloablative Agonists Antineoplastic Agents, Alkylating Antirheumatic Agents Alkylating Agents Immunosuppressive Agents Pharmacologic Actions |
