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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


Phase 1
21 Years
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

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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 - MiamiMiami, Florida  33136