A Phase I Trial of ZD1694 (TOMUDEX® (Registered Trademark)), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease
ZD1694 (TOMUDEX)
Néoplasmes
Étude thérapeutique
Résumé
Date de début de l'étude : 1 septembre 1993
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.60 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
National Cancer Institute (NCI)
Bethesda, United StatesOuvrir National Cancer Institute (NCI) dans Google Maps