5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in People With Advanced Solid Tumors

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT03366116
Phase
PHASE1
Status
Recruiting
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Conditions

  • Neoplasms
  • Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • aza-TdC — DRUG
    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 5-aza-4'-thio-2'- deoxycytidine (Aza-TdC) is incorporated into DNA, where it engages the active site of DNA methyltransferase I (DNMT1), a maintenance methyltransferase that contributes to hypermethylation and silencing of tumor suppressor genes. Aza-TdC offers an improvement over traditional DNMT inhibitors via higher incorporation into DNA and lower cytotoxicity; Aza-TdC has greater antitumor activity than another recently developed DNMT1 inhibitor, TdCyd, in some solid tumor xenograft models. Treatment with Aza-TdC is anticipated to yield inhibition of tumor growth due to DNMT1 depletion at oral doses that are well tolerated in extended dosing schedules.

Study Details

Background: Blood, tissue, and tumor cells contain genes. Genes are made up of DNA. DNA is the "instruction book" for each cell. In some people with cancer, the genes that might have slowed the growth of their tumor were "turned off." Researchers want to see if a new drug can turn the genes back on and slow the tumor growth. The drug is called Aza-TdC. Objective: To test the safety of Aza-TdC, and to find out the dose of this drug that can be safely given to humans. Eligibility: People ages 18 and older who have advanced cancer that has gotten worse after standard treatment, or for which no effective therapy exists Design: Participants will be screened with: Medical history Blood and urine tests Scans to measure their tumors Test to measure the electrical activity of the heart Participants will take the study drug by mouth. The drug is given in cycles. Each cycle is 21 days (3 weeks) long. Week 1 and week 2: participants will take the study drug once a day for 5 days. Then they will have 2 days without the drug. Week 3: no study drug is taken. This completes one cycle of treatment. For cycle 1, participants will repeat the screening tests several times. For all other cycles, participants will have blood tests and pregnancy tests. They will have scans of their tumor every 6 weeks. The cycle will be repeated as long as the participant tolerates the drug and the cancer is either stable or gets better. Sponsoring Institute: National Cancer Institute

Key Dates

Start date
Nov 5, 2018
Status verified
Jan 2026
Primary completion
Sep 30, 2026
Completion
Sep 30, 2026

Study Design

Enrollment
65 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: 1
    Aza-TdCyd will be administered orally once a day for 5 days of each week for 2 weeks, with one week off, in 21-day cycles

Primary Outcome Measure

To determine the safety, tolerability, and MTD of oral aza-TdCyd administered daily for 5 days a week for 2 weeks, with one week off, in 21-day cycles [ Time Frame: Cycle 1 and Cycle 2 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
888-624-1937

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By research site
National Institutes of Health Clinical Center· Bethesda, MD

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