A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
ZD1694 (TOMUDEX)
Neoplasms
Treatment Study
Summary
Study start date: September 1, 1993
Actual date on which the first participant was enrolled.Thymidylate synthase (TS), an enzyme which acts by utilizing 5,10-CH(2)FH(4) in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is a potential chemotherapeutic target. ZD1694 is a new quinazolone folate analog that directly inhibits TS. This phase I trial and pharmacokinetic study will describe and define the toxicities, determine the MTD, and describe the plasma pharmacokinetics of ZD1694 in pediatric patients with refractory cancer. The starting dose for this trial will be 2.0 mg/m(2) administered as a 15 minute IV infusion every 21 days.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.60 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.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Histologically proven malignancy considered refractory to standard therapy. Objective evidence of progression on prior therapy required. No leukemia. Bone marrow involvement by tumor acceptable. Marrow biopsy required if there is a history of involvement or peripheral counts are inadequate. PRIOR/CONCURRENT THERAPY: Biologic Therapy: Recovery from toxic effects of prior immunotherapy required. Chemotherapy: No more than 2 prior chemotherapy regimens and recovered. At least 2 weeks since myelosuppressive therapy (6 weeks since nitrosoureas). Endocrine Therapy: Not specified. Radiotherapy: No prior central axis irradiation (i.e., skull, spine, ribs, pelvis). Recovery from toxic effects of prior radiotherapy required. Surgery: Not specified. Other: No prior bone marrow transplantation. PATIENT CHARACTERISTICS: Age: 21 and under. Performance status: ECOG 0-2. Life expectancy: At least 8 weeks. Hematopoietic: (unless histologic evidence of bone marrow involvement by tumor). AGC at least 1,500/mm3. Platelet count at least 100,000/mm3. Hemoglobin at least 8.0 g/dL. Prior transfusion acceptable. Hepatic: Bilirubin no greater than 2 times normal. ALT no greater than 2 times normal. Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min/1.73 sqm. Cardiovascular: Not specified. Pulmonary: Not specified. OTHER: No significant accumulation of third space fluid. No significant systemic illness (e.g., infection). No pregnant or nursing women. Pregnancy test required in fertile women. All patients or their guardians must sign an informed consent.
Study 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 1 location
National Cancer Institute (NCI)
Bethesda, United StatesOpen National Cancer Institute (NCI) in Google Maps