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

Primary Purpose

Brain and Central Nervous System Tumors

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cytochlor

Tetrahydrouridine

Radiation Therapy

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult tumors metastatic to brain

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CldC + H4U

Arm Description

Outcomes

Primary Outcome Measures

To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.

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.

Secondary Outcome Measures

a) Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with CldC + H4U.

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 3

Cytochlor and metabolite levels in urine at weeks 1, 2, and 3

Full Information

NCT ID

NCT00521183

First Posted

August 24, 2007

Last Updated

November 24, 2014

Sponsor

Brian Lally

1. Study Identification

Unique Protocol Identification Number

NCT00521183

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Brian Lally

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain and Central Nervous System Tumors

Keywords

adult tumors metastatic to brain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CldC + H4U

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Cytochlor

Other Intervention Name(s)

CldC, CDC

Intervention Description

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

Intervention Name(s)

Tetrahydrouridine

Other Intervention Name(s)

THU, H4U

Intervention Description

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

Radiation

Intervention Name(s)

Radiation Therapy

Intervention Description

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

Primary Outcome Measure Information:

Title

To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.

Time Frame

2 Years

Title

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.

Time Frame

Duration of study treatment

Secondary Outcome Measure Information:

Title

a) Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with CldC + H4U.

Description

Time Frame

At protocol specified timepoints during treatment

Title

Cytochlor and metabolite levels in serum at weeks 1, 2, and 3

Time Frame

Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment

Title

Cytochlor and metabolite levels in urine at weeks 1, 2, and 3

Time Frame

Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fazilat Ishkanian, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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