NCT00521183

Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Brian Lally · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as cytochlor and tetrahydrouridine, may make tumor cells more sensitive to radiation therapy. PURPOSE: This phase I trial is studying the side effects and best dose of cytochlor when given together with tetrahydrouridine and external-beam radiation therapy in treating patients with cancer that has spread to the brain.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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 thereafter.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	Cytochlor	The study's starting dose of CldC is 50 mg/m2/day. The dose of CldC will be escalated / de-escalated for patients. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.
DRUG	Tetrahydrouridine	A fixed dose of H4U at 720 mg/m2/day will be used, regardless of the dose of CldC administered. H4U will be delivered by an IV bolus infusion over a period of 5 minutes, followed 5 minutes later by an IV bolus infusion of CldC. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.
RADIATION	Radiation Therapy	One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.

Timeline

• Start date: 2007-06-01
• Primary completion: 2014-05-01
• Completion: 2014-05-01
• First posted: 2007-08-27
• Last updated: 2014-11-25

Locations

1 site across 1 country: United States