Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With a Fixed Dose of Cisplatin Concomitant With Definitive Radiation in Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity and Oropharynx
cisplatin
+ cytochlor
+ tetrahydrouridine
Carcinome épidermoïde de la tête et du cou+5
+ Carcinome
+ Carcinome à cellules squameuses
Étude thérapeutique
Résumé
Date de début de l'étude : 1 avril 2004
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: Primary * Determine the dose range of cytochlor to be used in phase II trials, based on safety, toxicity, and tissue selectivity, in patients with advanced squamous cell carcinoma of the oral cavity or oropharynx. * Determine the safety and toxicity profile of cytochlor, tetrahydrouridine, and concurrent radiotherapy followed by radiotherapy alone in these patients. * Determine the percentage of cancer cells vs normal cells that incorporate cytochlor in the DNA of patients treated with this regimen. * Determine the percentage replacement of thymine by 5-chlorouracil in tumors vs normal tissue of patients treated with this regimen. Secondary * Determine the tissue selectivity of this regimen in these patients. * Determine the level of cytochlor and its metabolites within the serum and urine of these patients during combination treatment and before radiotherapy alone is initiated. * Determine the pharmacokinetics of this regimen in these patients. OUTLINE: This is an open-label, dose-escalation study of cytochlor. Patients receive tetrahydrouridine IV over 5 minutes followed by cytochlor IV for 3 days on week 1 and 5 days a week on weeks 2-4 and cisplatin IV over 30-60 minutes once in weeks 2 and 5. Patients also undergo radiotherapy 5 days a week during weeks 2-7. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cytochlor until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed at 1 month, monthly for 3 months, every 3 months for up to 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2 years.
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.1 participant 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.De 21 à 120 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.Conditions
Pathologie
Critères
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity or oropharynx * Stage III disease not eligible for surgery * Stage IV disease allowed if patient is not eligible for chemotherapy or refused chemotherapy * No distant metastasis * Previously untreated disease * No osteoradionecrosis in patients with tumors involving the maxilla * Tumor tissue/normal adjacent tissue (T/N) ratio for dC kinase and dCMP deaminase greater than 2.5 PATIENT CHARACTERISTICS: Age * Over 21 Performance status * Karnofsky 80-100% OR * ECOG 0-1 Life expectancy * More than 6 months Hematopoietic * Absolute neutrophil count greater than 1,500/mm\^3 * WBC at least 3,000/mm\^3 * Platelet count greater than 100,000/mm\^3 Hepatic * AST/ALT less than 2.5 times upper limit of normal * Bilirubin normal Renal * Creatinine normal OR * Creatinine clearance greater than 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No impending carotid rupture Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after study treatment * HIV negative * No other concurrent uncontrolled illness * No active or ongoing infection * No alcohol dependence * No psychiatric illness or social situation that would preclude study compliance * No other malignancy within the past 3 years except low-risk, non-melanomatous skin cancer, carcinoma in situ (e.g., breast, cervix, or bladder), or stage T1-2, low-to-moderate grade prostate cancer (Gleason score no greater than 7) PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy Chemotherapy * See Disease Characteristics * No other concurrent chemotherapy Endocrine therapy * No concurrent hormonal therapy except contraceptives or replacement steroids Radiotherapy * Not specified Surgery * See Disease Characteristics Other * No prior therapy for head and neck cancer * No other concurrent experimental medications * No other concurrent anticancer therapy * No concurrent combination antiretroviral therapy for HIV-positive patients
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalCentres 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
University of Miami Sylvester Comprehensive Cancer Center
Miami, United StatesOuvrir University of Miami Sylvester Comprehensive Cancer Center dans Google Maps