- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00521183
Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Miami, Florida, United States, 33136
- University of Miami
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CldC + H4U
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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.
Other Names:
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.
Other Names:
One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.
Time Frame: 2 Years
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2 Years
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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
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Duration of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
a) Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with CldC + H4U.
Time Frame: At protocol specified timepoints during treatment
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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
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At protocol specified timepoints during treatment
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Cytochlor and metabolite levels in serum at weeks 1, 2, and 3
Time Frame: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
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Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
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Cytochlor and metabolite levels in urine at weeks 1, 2, and 3
Time Frame: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
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Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Fazilat Ishkanian, MD, University of Miami
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20057104
- SCCC-2005097 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)
- WIRB-20051340 (Other Identifier: Western Institutional Review Board)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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