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 Comcomitant With Definitive Radiation in Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity and Oropharynx
- 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.
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Luis E. Raez, MD, FACP
University of Miami Sylvester Comprehensive Cancer Center
United States: Food and Drug Administration
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