FdCyd and THU for Advanced Solid Tumors

NCT01534598 | Completed Phase 1 FDA Drug

• 2 other identifiers: 12006612-C-0066
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Neoplasms

Keywords

DNA Methylation; Advanced Cancer; Methyltransferase Inhibitor; Epigenetics; Gene Re-Expression

Outcome Measures

Primary Outcomes (1)

• 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.

  1 cycle

Study Arms (1)

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.

Drug: FdCyd + THU

Interventions

FdCyd + THU DRUG

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.

Single Arm

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

UC Davis Cancer Center

Sacramento, California, 95817, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Penn State

Hershey, Pennsylvania, 17033, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms

Interventions

5-fluoro-2'-deoxycytidine; Tetrahydrouridine

Intervention Hierarchy (Ancestors)

Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• James H Doroshow, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: February 16, 2012
• Study Start: March 5, 2012
• Primary Completion: October 7, 2019
• Study Completion: July 21, 2025
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

US (6)