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COMPLETED
NCT02423057
PHASE1

Phase I Trial of 4'-Thio-2'-Deoxycytidine (TdCyd) in Patients With Advanced Solid Tumors

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

Background: \- Genes are made up of DNA and are the instruction book for cells. When people have cancer, some of the genes that might have slowed the growth of tumor cells were turned off. Researchers think a drug called TdCyd might help to turn these genes back on. This may slow the growth of tumors in people with cancer. Objectives: \- To test the safety of TdCyd and to find out how it works. Also, to find out the dose of the drug that can be safely given to humans. Eligibility: \- Adults 18 years and older who have advanced cancer that has progressed after standard treatment, or for which no effective therapy exists. Design: * Participants will take TdCyd by mouth. The drug is given in 21-day cycles. TdCyd is taken once a day during week 1 for 5 days. Then for 2 days participants do not take the drug. Then they take it for 5 days during week 2. No TdCyd is taken during week 3. * Participants will keep a diary of their study drug doses. * Participants will have tests about every 3 weeks to see how the study drugs are affecting their body. They will have blood and urine tests, a medical history, and physical exams. They may have computed tomography (CT) scans to measure their tumors. They may have an electrocardiogram, which measures the heart electrical activity. * If participants develop any side effects, they may be asked to visit more often. * Participants will stay in the study as long as they are tolerating TdCyd and their tumors are either stable or getting better. One month after stopping the drug, they will have a follow-up phone call.

Key Details

Gender

All

Age Range

18 Years - 120 Years

Study Type

INTERVENTIONAL

Enrollment

27

Start Date

2015-05-18

Completion Date

2025-07-21

Last Updated

2026-04-24

Healthy Volunteers

No

Interventions

DRUG

TdCyd

Methylation-mediated silencing of genes is an epigenetic mechanism implicated in carcinogenesis; agents that inhibit this mechanism are of clinical interest because of their potential to re-activate silenced tumor suppressor genes. The nucleoside analog 4'-thio-2'-deoxycytidine (TdCyd) is incorporated into DNA where it engages the active site of DNA methyltransferase I (DNMT1), a maintenance methyltransferase that contributes to the hypermethylation and silencing of tumor suppressor genes. TdCyd offers an improvement over current DNMT inhibitors by virtue of a higher incorporation rate into DNA at lower levels of cytotoxicity; treatment with TdCyd is anticipated to result in the inhibition of tumor growth due to DNMT1 depletion at oral doses that are well tolerated in extended dosing schedules.

Locations (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States