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

Phase 1
Completed
Conditions
Brain and Central Nervous System Tumors
Interventions
Radiation: Radiation Therapy
Registration Number
NCT00521183
Lead Sponsor
Brian Lally
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CldC + H4URadiation Therapy-
CldC + H4UCytochlor-
CldC + H4UTetrahydrouridine-
Primary Outcome Measures
NameTimeMethod
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.2 Years
b) Establish the safety and toxicity profile of CldC+ H4U when given in combination with RT for 2 weeks following treatment with the drug alone for 3 days in the week prior to the combined treatment.Duration of study treatment
Secondary Outcome Measures
NameTimeMethod
Cytochlor and metabolite levels in urine at weeks 1, 2, and 3Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
a) Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with CldC + H4U.At protocol specified timepoints during treatment

Baseline Levels of CD will be obtained by assaying CD in serum prior to initiation of treatment on Wednesday of week 1. Follow-up assays of CD in serum will be made on the Fridays of weeks 1 to 3 after each day's treatment with CldC + H4U. In weeks 2 and 3 this will take place prior to RT

Cytochlor and metabolite levels in serum at weeks 1, 2, and 3Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment

Trial Locations

Locations (1)

University of Miami

🇺🇸

Miami, Florida, United States

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