5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in People With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03366116|
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : September 22, 2021
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.
To test the safety of Aza-TdC, and to find out the dose of this drug that can be safely given to humans.
People ages 18 and older who have advanced cancer that has gotten worse after standard treatment, or for which no effective therapy exists
Participants will be screened with:
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
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms Solid Tumors||Drug: aza-TdC||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of 5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in Patients With Advanced Solid Tumors|
|Actual Study Start Date :||November 5, 2018|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||September 30, 2022|
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
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.
- 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 ]To determine the safety, tolerability, and MTD of oral aza-TdC administered daily for 5 days a week for 2 weeks, with one week off, in 21-day cycles
- To determine the pharmacokinetics of oral aza-TdCyd [ Time Frame: Cycle 1 ]To determine the pharmacokinetics of oral aza-TdC
- To document preliminary evidence of aza-TdCyd activity [ Time Frame: Cycle 1 and 2 ]To document preliminary evidence of aza-TdC activity
- To determine effect of study treatment on re-expression of select genes silenced by methylation in circulating tumor cells [ Time Frame: Cycle 1 and 2 ]To determine effect of study treatment on re-expression of select genes silenced by methylation in circulating tumor cells
- To determine the effects of Aza-TdC on DNA damage response (DDR) signaling and on genome-wide DNA methylation in tumor biopsy tissue [ Time Frame: Pre-treatment, Cycle 1 Day 2, Cycle 2 Day 10 ]To determine the effects of Aza-TdC on DNA damage response (DDR) signaling and on genome-wide DNA methylation in tumor biopsy tissue
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366116
|Contact: Ashley B Bruns||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||James H Doroshow, M.D.||National Cancer Institute (NCI)|