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
Squamous Cell Carcinoma of Head and Neck+5
+ Carcinoma
+ Carcinoma, Squamous Cell
Treatment Study
Summary
Study start date: April 1, 2004
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.1 patient 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.From 21 to 120 Years
Range of ages for which participants are eligible to join.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 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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy 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
University of Miami Sylvester Comprehensive Cancer Center
Miami, United StatesOpen University of Miami Sylvester Comprehensive Cancer Center in Google Maps