NeoplasmsPhase 1NCT01534598
FdCyd and THU for Advanced Solid Tumors
A Phase 1 study testing FdCyd + THU in people with Neoplasms, run by National Cancer Institute (NCI) at 6 sites in United States.
Trial summary
Background: FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are experimental cancer treatment drugs. FdCyd may change how genes work in cancer cells. THU helps keep FdCyd from being broken down by the body. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Neoplasms
- What is being tested?
- FdCyd + THU
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 6 sitesUnited States
- Study dates
- 5 Mar 2012to 21 Jul 2025
- 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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically documented solid tumors whose disease has progressed on standard therapy that is known to be associated with a survival advantage or have disease for which there is no known standard therapy.
- Patients must have measurable or evaluable disease.
- Diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is being enrolled prior to patient enrollment.
- Patients must have completed any chemotherapy, radiation therapy, biologic therapy, or major surgery greater than or equal to 4 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study, at the discretion of the Principal Investigator. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Patients with bone metastases or hypercalcemia on IV bisphosphonate treatment prior to study entry may continue this treatment.
- Age greater than or equal to18 years. Because no dosing or adverse event data are currently available on the use of FdCyd and THU in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.
- Karnofsky performance status greater than or equal to 60%.
Show all 23Show fewer
- Life expectancy of greater than 3 months.
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin less than or equal to 1.5 X institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) greater than or equal to 3 X institutional upper limit of normal
- creatinine less than 1.5 X institutional upper limit of normal
- OR
- creatinine clearance greater than or equal to 60 ML/min for patients with creatinine levels above 1.5 X institutional upper limit of normal
- Because FdCyd has been shown to be teratogenic in animals, pregnant women are excluded from this trial. Nursing women are also excluded, as there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with FdCyd. Women of childbearing potential must agree to either abstain from sexual intercourse or use two forms of acceptable birth control, including one barrier method, for 4 weeks prior to study entry, for the duration of study participation, and for 3 months after completion of study. Men must use a latex condom every time they have sexual intercourse during therapy and for 3 months after study completion, even if they have had a successful vasectomy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she or her partner should inform the treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients should not be receiving any other investigational agents.
- Ability to swallow liquids.
- Willingness to provide blood and urine samples, and biopsy samples if on the expansion phase of the study, for research purposes. For the expansion cohort, patients must have tumor amenable to biospy (excisional or incision biopsies of skin or H \& N lesions under visualization) and willingness to undergo a tumor biopsy or patient will be undergoing a procedure due to medical necessity during which the tissue may be collected, or tumor biopsy tissue from a previous research study or medical care is available for submission at registration. Criteria for the submission of tissue are:
- Tissue must have been collected within 3 months prior to registration
- Patient has not received any intervening therapy for their cancer since the collection of the tumor sample
- Tumor tissue must meet the minimum requirements
Who cannot join
- Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, known HIV infection requiring protease inhibitor therapy, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 2 months after treatment of the brain metastases. Patients should be on stable doses of anti-seizure medications. These patients may be enrolled at the discretion of the Principal Investigator.
- History of allergic reactions attributed to fluoropyrimidines (e.g., capecitabine, fluorouracil, fluorodeoxyuridine) or tetrahydrouridine.
- Malabsorption syndrome or other conditions that would interfere with intestinal absorption.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
City of Hope
Duarte, California, 91010
Penn State
Hershey, Pennsylvania, 17033
USC Norris Cancer Center
Los Angeles, California, 90033
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
UC Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase I Trial of Oral 5-Fluoro-2'-Deoxycytidine With Oral Tetrahydrouridine in Patients With Advanced Solid Tumors
Background:
- FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are experimental cancer treatment drugs. FdCyd may change how genes work in cancer cells. THU helps keep FdCyd from being broken down by the body. FdCyd and THU have been given to people on other cancer treatment trials, usually by vein. Researchers want to give FdCyd and THU by mouth to see if they work against cancers that have not responded to earlier treatments.
Read more
Objectives:
- To test oral FdCyd and THU on advanced solid tumors that have not responded to earlier treatments.
Eligibility:
- Individuals at least 18 years of age who have advanced solid tumors that have not responded to standard treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor samples will used to study the cancer before treatment.
- FdCyd and THU will be given in 21-day cycles. THU should be taken 30 minutes before taking FdCyd.
- Participants will take FdCyd and THU by mouth, once a day, for 3 days at the beginning of the first and second weeks of each cycle (days 1 3 and 8 10). The drugs will not be taken during the entire third week of each cycle.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Treatment will continue as long as the cancer is responding to the drugs and serious side effects do not develop.
Read the detailed description
Background:
- 5-Fluoro-2'-deoxycytidine (FdCyd), a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the AUC of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into DNA and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
- Intravenous FdCyd with THU has been evaluated in a Phase I clinical trial with some preliminary evidence of activity. This trial will investigate oral administration of the drugs, which was shown to be feasible in an expansion cohort of the previous trial.
Primary objectives:
-Establish the safety and tolerability of oral FdCyd in combination with oral THU administered on an intermittent schedule in 21-day cycles to patients with refractory solid tumors
Exploratory objectives:
- Determine the pharmacokinetics of oral FdCyd and oral THU
- Document preliminary evidence of activity of oral FdCyd and oral THU
- Determine the clinical benefit rate (CR+PR+SD at 4 months) in patients treated with study drug combination at the MTD
- Determine effect of study treatment on re-expression of p16 and other select genes silenced by methylation in circulating tumor cells and tumor biopsies
- Evaluate the effect of study treatment on DNA (cytosine-5)-methyltransferase 1 and 3 (DNMT1 and DNMT3) expression in tumor biopsies
Eligibility:
-Adults with histologically documented solid tumors whose disease has progressed after at least one line of standard therapy.
Design:
- This is a multicenter trial with NCI as the coordinating center.
- FdCyd and THU will be administered on an intermittent schedule in 21-day cycles. THU will be administered orally 30 minutes prior to FdCyd.
- The trial will follow a standard Phase I dose escalation design (3-6 patients per cohort).
- Consideration will be given to increasing the days of administration of FdCyd with THU after a target maximum plasma concentration of FdCyd is reached.
- Blood and urine for pharmacokinetic studies will be obtained from all patients. Blood for pharmacodynamic studies will be obtained after we achieve a target Cmax of 1microM.
- Up to 25 patients will be enrolled in the expansion cohort, from which mandatory pre- and post-dose tumor biopsies will be collected for the assessment of pharmacodynamic endpoints, at dose level 8 (160 mg FdCyd + 3000 mg THU 1x daily days 1-6 week 1, days 8-13 week 2, in 21-day cycles).
- Conditions
- Neoplasms
- Being tested
- FdCyd + THU
- Keywords
- DNA Methylation, Advanced Cancer, Methyltransferase Inhibitor, Epigenetics, Gene Re-Expression
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FdCyd + THUDrug
Intravenous FdCyd with THU has been evaluated in a Phase I clinical trial with some preliminary evidence of activity. This trial will investigate oral administration of the drugs, which was shown to be feasible in an expansion cohort of the previous trial.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | FdCyd + THU administered on an intermittent schedule in 21-day cycles per dose escalation table. THU will be administered orally at a fixed dose of 3000 mg 30 minutes prior to FdCyd. Receives: Drug: FdCyd + THU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
FdCyd + THU administered on an intermittent schedule in 21-day cycles per dose escalation table. THU will be administered orally at a fixed dose of 3000 mg 30 minutes prior to FdCyd.
Measured: 1 cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2012 (estimated)
- Study start5 Mar 2012
- Primary completion7 Oct 2019
- Study completion21 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James H Doroshow, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01534598
- Sponsor's protocol ID
- 120066
- Other IDs
- 12-C-0066
- Status last verified
- Feb 2026
- First submitted
- 15 Feb 2012
- Last updated
- 10 Feb 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Oral 5-Fluoro-2'-Deoxycytidine With Oral Tetrahydrouridine in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01534598
- Acronym / sponsor ID
- 120066
- Conditions
- Neoplasms
- Keywords
- DNA Methylation, Advanced Cancer, Methyltransferase Inhibitor, Epigenetics, Gene Re-Expression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 5 Mar 2012 (actual)
- Primary completion
- 7 Oct 2019 (actual)
- Study completion
- 21 Jul 2025 (actual)
- First posted
- 16 Feb 2012 (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.
Background:
- FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are experimental cancer treatment drugs. FdCyd may change how genes work in cancer cells. THU helps keep FdCyd from being broken down by the body. FdCyd and THU have been given to people on other cancer treatment trials, usually by vein. Researchers want to give FdCyd and THU by mouth to see if they work against cancers that have not responded to earlier treatments.
Objectives:
- To test oral FdCyd and THU on advanced solid tumors that have not responded to earlier treatments.
Eligibility:
- Individuals at least 18 years of age who have advanced solid tumors that have not responded to standard treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor samples will used to study the cancer before treatment.
- FdCyd and THU will be given in 21-day cycles. THU should be taken 30 minutes before taking FdCyd.
- Participants will take FdCyd and THU by mouth, once a day, for 3 days at the beginning of the first and second weeks of each cycle (days 1 3 and 8 10). The drugs will not be taken during the entire third week of each cycle.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Treatment will continue as long as the cancer is responding to the drugs and serious side effects do not develop.
Detailed description
Background:
- 5-Fluoro-2'-deoxycytidine (FdCyd), a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the AUC of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into DNA and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
- Intravenous FdCyd with THU has been evaluated in a Phase I clinical trial with some preliminary evidence of activity. This trial will investigate oral administration of the drugs, which was shown to be feasible in an expansion cohort of the previous trial.
Primary objectives:
-Establish the safety and tolerability of oral FdCyd in combination with oral THU administered on an intermittent schedule in 21-day cycles to patients with refractory solid tumors
Exploratory objectives:
- Determine the pharmacokinetics of oral FdCyd and oral THU
- Document preliminary evidence of activity of oral FdCyd and oral THU
- Determine the clinical benefit rate (CR+PR+SD at 4 months) in patients treated with study drug combination at the MTD
- Determine effect of study treatment on re-expression of p16 and other select genes silenced by methylation in circulating tumor cells and tumor biopsies
- Evaluate the effect of study treatment on DNA (cytosine-5)-methyltransferase 1 and 3 (DNMT1 and DNMT3) expression in tumor biopsies
Eligibility:
-Adults with histologically documented solid tumors whose disease has progressed after at least one line of standard therapy.
Design:
- This is a multicenter trial with NCI as the coordinating center.
- FdCyd and THU will be administered on an intermittent schedule in 21-day cycles. THU will be administered orally 30 minutes prior to FdCyd.
- The trial will follow a standard Phase I dose escalation design (3-6 patients per cohort).
- Consideration will be given to increasing the days of administration of FdCyd with THU after a target maximum plasma concentration of FdCyd is reached.
- Blood and urine for pharmacokinetic studies will be obtained from all patients. Blood for pharmacodynamic studies will be obtained after we achieve a target Cmax of 1microM.
- Up to 25 patients will be enrolled in the expansion cohort, from which mandatory pre- and post-dose tumor biopsies will be collected for the assessment of pharmacodynamic endpoints, at dose level 8 (160 mg FdCyd + 3000 mg THU 1x daily days 1-6 week 1, days 8-13 week 2, in 21-day cycles).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: FdCyd + THUFdCyd + THU administered on an intermittent schedule in 21-day cycles per dose escalation table. THU will be administered orally at a fixed dose of 3000 mg 30 minutes prior to FdCyd. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients must have histologically documented solid tumors whose disease has progressed on standard therapy that is known to be associated with a survival advantage or have disease for which there is no known standard therapy.
- Patients must have measurable or evaluable disease.
- Diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is being enrolled prior to patient enrollment.
- Patients must have completed any chemotherapy, radiation therapy, biologic therapy, or major surgery greater than or equal to 4 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study, at the discretion of the Principal Investigator. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Patients with bone metastases or hypercalcemia on IV bisphosphonate treatment prior to study entry may continue this treatment.
- Age greater than or equal to18 years. Because no dosing or adverse event data are currently available on the use of FdCyd and THU in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.
Key exclusion criteria (4 listed)
- Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, known HIV infection requiring protease inhibitor therapy, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 2 months after treatment of the brain metastases. Patients should be on stable doses of anti-seizure medications. These patients may be enrolled at the discretion of the Principal Investigator.
- History of allergic reactions attributed to fluoropyrimidines (e.g., capecitabine, fluorouracil, fluorodeoxyuridine) or tetrahydrouridine.
- Malabsorption syndrome or other conditions that would interfere with intestinal absorption.
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 |
|---|---|---|
| FdCyd + THUIntravenous FdCyd with THU has been evaluated in a Phase I clinical trial with some preliminary evidence of activity. This trial will investigate oral administration of the drugs, which was shown to be feasible in an expansion cohort of the previous trial. | Drug | Single Arm |
Primary outcome
Safety and tolerability
Time frame: 1 cycle
FdCyd + THU administered on an intermittent schedule in 21-day cycles per dose escalation table. THU will be administered orally at a fixed dose of 3000 mg 30 minutes prior to FdCyd.
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 10 Feb 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
James H Doroshow, M.D. principal investigator
National Cancer Institute (NCI)
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FdCyd + THU in people with Neoplasms, run by National Cancer Institute (NCI) at 6 sites 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 23 inclusion and 4 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 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
Safety and tolerability (time frame: 1 cycle). 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 10 Feb 2026.