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
21 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
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
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of metastatic cancer to the brain by contrast-enhanced MRI or CT scan
- Eligible for whole-brain radiotherapy (WBRT)
- Patients treated with prior surgery are eligible if WBRT is to be used post
operatively
- Not planning to be treated with stereotactic radiosurgery
- No leptomeningeal metastasis documented by contrast-enhanced MRI/CT scan or
cerebrospinal fluid evaluation
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status (PS) 70-100% or ECOG PS 0-1
- Leukocytes ≥ 3,000/µL
- Absolute neutrophil count > 1,500/µL
- Platelet count > 100,000/µL
- Total bilirubin normal
- AST and ALT < 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance > 60 mL/min
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation
Exclusion criteria:
- Uncontrolled intercurrent illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Pregnant or lactating
- Alcohol dependence
PRIOR CONCURRENT THERAPY:
- No prior radiotherapy to the brain
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent chemotherapy, immunotherapy, hormonal therapy (excluding
contraceptives and replacement steroids), or other experimental medication
- No other concurrent anticancer therapy outside the protocol
- Systemic therapy one month before or after brain radiotherapy is allowed
- No concurrent heparin or coumadin
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.
Outcome Time Frame:
2 Years
Safety Issue:
No
Principal Investigator
Brian Lally, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Miami Sylvester Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
EPROST-20057104
NCT ID:
NCT00521183
Start Date:
June 2007
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult tumors metastatic to brain
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida 33136 |
