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

NCT ID: NCT00521183

Last Updated: 2014-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2014-05-31

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CldC + H4U

Group Type: EXPERIMENTAL

Cytochlor

Intervention Type: DRUG

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.

Tetrahydrouridine

Intervention Type: DRUG

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 Therapy

Intervention Type: RADIATION

One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

CldC, CDC; THU, H4U

Eligibility Criteria

Inclusion Criteria

• 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:

• 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brian Lally

OTHER

Sponsor Role: lead

Responsible Party

Brian Lally

Assistant Professor of Clinical

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Fazilat Ishkanian, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

SCCC-2005097

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB-20051340

Identifier Type: OTHER

Identifier Source: secondary_id

20057104

Identifier Type: -

Identifier Source: org_study_id