Phase I Pharmacokinetic and Pharmacodynamic Trial of Irinotecan in Combination With Tomudex in Patients With Refractory Solid Malignancies
irinotecan hydrochloride
+ raltitrexed
Étude thérapeutique
Résumé
Date de début de l'étude : 1 décembre 1997
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan in combination with raltitrexed in patients with refractory solid tumors. II. Describe and quantify the toxic effects of this combination treatment regimen in a minimally pretreated patient population. III. Determine the pharmacokinetics of this combination treatment regimen. IV. Document any antitumor activity of this combination treatment regimen in this patient population. OUTLINE: This is a dose escalation study of irinotecan and raltitrexed. Patients receive irinotecan IV over 90 minutes on days 1 and 8 followed by raltitrexed IV over 15 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of irinotecan and raltitrexed until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Additional cohorts receive raltitrexed on day 2 rather than day 1 near the final dose levels of the combination drugs. PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 1 year.
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.39 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.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Critères
DISEASE CHARACTERISTICS: Histologically proven malignant solid tumor that has failed prior conventional chemotherapy or for which no established therapy exists Recurrent or metastatic gastrointestinal adenocarcinoma with no prior therapy eligible No evidence of CNS metastases (brain or leptomeningeal disease) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,500/mm3 Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.8 mg/dL SGOT and SGPT less than 3 times upper limit of normal (ULN) Alkaline phosphatase less than 3 times ULN (5 times ULN for metastatic disease) Renal: Creatinine no greater than 1.8 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No congestive heart failure Other: No uncontrolled diabetes Not pregnant or nursing Negative pregnancy test No other serious medical illness (e.g. clinically active infectious process) No psychiatric illness precluding study No ascites or pleural effusion PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy and recovered No more than 1 prior adjuvant chemotherapy regimen No more than 1 prior chemotherapy regimen for recurrent or metastatic disease No prior irinotecan or raltitrexed At least 8 weeks since prior nitrosourea or mitomycin and recovered Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy and recovered Prior radiotherapy limited to no greater than 25% of bone marrow Surgery: Not specified
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