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

Brian Lally

Status and phase

Completed

Phase 1

Conditions

Brain and Central Nervous System Tumors

Treatments

Radiation: Radiation Therapy

Drug: Tetrahydrouridine

Drug: Cytochlor

Study type

Interventional

Funder types

Other

Identifiers

NCT00521183

WIRB-20051340 (Other Identifier)

SCCC-2005097 (Other Identifier)

20057104

Details and patient eligibility

About

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.

Full 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.

Enrollment

2 patients

Sex

All

Ages

21+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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