Brain and Central Nervous System TumorsPhase 1NCT00521183
Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain
A Phase 1 study testing Cytochlor, Tetrahydrouridine and Radiation Therapy in people with Brain and Central Nervous System Tumors, run by Brian Lally at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- Cytochlor, Tetrahydrouridine and Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to May 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Cytochlor, Tetrahydrouridine, Radiation Therapy
- Keywords
- adult tumors metastatic to brain
- Medical subject headings
- Central Nervous System Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytochlorDrug
Also called CldC, CDC
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.
TetrahydrouridineDrug
Also called THU, H4U
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 TherapyRadiation
One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.
| Study group | Role | What they receive |
|---|---|---|
| CldC + H4U | Experimental | Not described Receives: Drug: Cytochlor; Drug: Tetrahydrouridine; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.
Measured: 2 Years
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.
Measured: Duration of study treatment
Secondary outcomes (3)
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
Measured: At protocol specified timepoints during treatment
Cytochlor and metabolite levels in serum at weeks 1, 2, and 3
Measured: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
Cytochlor and metabolite levels in urine at weeks 1, 2, and 3
Measured: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2007 (estimated)
- Study startJun 2007
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brian Lally
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Brian Lally, University of Miami
- Investigators
- Fazilat Ishkanian, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00521183
- Sponsor's protocol ID
- 20057104
- Other IDs
- SCCC-2005097, WIRB-20051340
- Status last verified
- Nov 2014
- First submitted
- 24 Aug 2007
- Last updated
- 25 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00521183
- Acronym / sponsor ID
- 20057104
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult tumors metastatic to brain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Brian LallyUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 27 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CldC + H4U | Experimental | Drug: Cytochlor, Drug: Tetrahydrouridine, Radiation: Radiation Therapy |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Pregnant or lactating
- Alcohol dependence
- No prior radiotherapy to the brain
- No concurrent combination antiretroviral therapy for HIV-positive patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytochlorAlso: CldC, CDCThe 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. | Drug | CldC + H4U |
| TetrahydrouridineAlso: THU, H4UA 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. | Drug | CldC + H4U |
| Radiation TherapyOne treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks. | Radiation | CldC + H4U |
Primary outcome
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.
Time frame: 2 Years
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
3 secondary outcomes
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
Cytochlor and metabolite levels in serum at weeks 1, 2, and 3
Time frame: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
Cytochlor and metabolite levels in urine at weeks 1, 2, and 3
Time frame: Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fazilat Ishkanian, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytochlor, Tetrahydrouridine and Radiation Therapy in people with Brain and Central Nervous System Tumors, run by Brian Lally at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity. (time frame: 2 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2014.