Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With External Brain Radiation for Metastatic Carcinoma to the Brain
- Establish the safety and toxicity profile of cytochlor and H4U when given in
combination with external-beam radiotherapy for 2 weeks after treatment with the drugs
alone in the previous week.
- Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during
the course of treatment with cytochlor and H4U.
- Perform detailed pharmacokinetic studies to determine the levels of cytochlor and its
metabolites in serum and in urine in weeks 1, 2, and 3 during treatment.
OUTLINE: This is a dose-escalation study of cytochlor.
Patients receive cytochlor IV and tetrahydrouridine (H4U) IV over 5 minutes on 3 days in
week 1 and on days 1-5 in weeks 2 and 3. Patients also undergo external-beam radiotherapy 5
days a week in weeks 2 and 3 initiated 3-4 hours after infusions of cytochlor and H4U.
Treatment may repeat in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed monthly for 3 months, every 3
months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then yearly
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.
Brian Lally, MD
University of Miami Sylvester Comprehensive Cancer Center
United States: Food and Drug Administration
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