Clinical trial · Interventional
5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in People With Advanced Solid Tumors
Phase I Trial of 5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in Patients With Advanced Solid Tumors
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 26, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260926-000001
Summary
Brief summary (as posted)
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
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Neoplasms | Neoplasm | ONTOLOGY_EXACT | 0.90 |
| Solid Tumors | Solid Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| aza-TdC | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- 1
- description
- 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
- interventionNames
- Drug: aza-TdC
Primary outcomes (1)
- 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
- timeFrame
- Cycle 1 and Cycle 2
- description
- 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
Secondary outcomes (4)
- measure
- To determine the pharmacokinetics of oral aza-TdCyd
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 120 Years
Show eligibility criteria text
* INCLUSION CRITERIA:
* Patients must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy.
* Age \>=18 years of age.
* ECOG performance status \<= 2.
* Patients must have normal organ and marrow function as defined below:
* absolute neutrophil count \>= 1,500/mcL
* platelets \>=100,000/mcL
* total bilirubin \<=1.5 X institutional upper limit of normal (\<=3 x upper limit of normal in the presence of documented Gilbert s syndrome)
* AST(SGOT)/ALT(SGPT) \<=3 X institutional upper limit of normal
OR
* AST(SGOT)/ALT(SGPT) \<=5 X institutional upper limit of normal for patients with liver metastases
* creatinine \<=1.5X institutional upper limit of normal
OR
* creatinine clearance \>=60 mL/min/1.73 m\^2 for patients with creatinine levels above 1.5X institutional normal
* Because nucleoside analogs are known to be teratogenic, women of child-bearing potential and men must agree to use two forms of contraception (hormonal or barrier method of birth control; abstinence; sterilization) prior to study entry, for the duration of study participation, and for 3 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use two forms of contraception prior to the study, for the duration of study participation, and for 3 months after completion of administration of Aza-TdC.
* Patients must have completed any chemotherapy or biologic therapy \>= 4 weeks or 5 half-lives (whichever is shorter) (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Patients must be \>= 2 weeks since any prior palliative radiation or cyberknife therapy. Patients must have recovered to grade 1 from prior toxicity or adverse events. Patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI's discretion. Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment prior to study entry may continue this treatment.
* Ability to understand and the willingness to sign a written informed consent document.
* Willingness to provide blood and urine samples for research purposes.
* Ability to swallow pills/capsules.
* Left ventricular ejection fraction greater than 45% or the institutional lower limit of normal by either ECHO or MUGA at entry.
* For patients enrolled on the expansion cohort, patients must have tumor amenable to biopsy (excisional or incision biopsies of skin or H \& N lesions under visualization) and willingness to undergo tumor biopsies.
EXCLUSION CRITERIA:
* Patients who are receiving any other investigational agents.
* Pregnant women and women who are breastfeeding are excluded from this study.
* 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, known Hepatitis B, known 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 primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
* Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
* Evaluable or measurable disease outside the CNS
* No metastases to brain stem, midbrain, pons, medulla, or cerebellum
* No history of intracranial hemorrhage or spinal cord hemorrhage
* No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
* No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1
* Patients with treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
* No stereotactic radiation or whole-brain radiation within 14 days prior to Cycle 1, Day 1
* Screening CNS radiographic study 2 weeks from completion of radiotherapy and \>=1 week from discontinuation of corticosteroids. The presence of new CNS mets will not exclude the patient but provide a baseline. If the irradiated lesion showed increased edema or growth, patient may be enrolled if asymptomatic but a repeat MRI should be done within the next 2-4 weeks for follow up.
* Malabsorption syndrome or other conditions that would interfere with intestinal absorption.References
Publications (3)
- BACKGROUNDCowan LA, Talwar S, Yang AS. Will DNA methylation inhibitors work in solid tumors? A review of the clinical experience with azacitidine and decitabine in solid tumors. Epigenomics. 2010 Feb;2(1):71-86. doi: 10.2217/epi.09.44. PMID 22122748
- BACKGROUNDThottassery JV, Sambandam V, Allan PW, Maddry JA, Maxuitenko YY, Tiwari K, Hollingshead M, Parker WB. Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4'-thio-2'-deoxycytidine and 5-aza-4'-thio-2'-deoxycytidine. Cancer Chemother Pharmacol. 2014 Aug;74(2):291-302. doi: 10.1007/s00280-014-2503-z. Epub 2014 Jun 8. PMID 24908436
- BACKGROUNDTiwari KN, Cappellacci L, Montgomery JA, Secrist JA 3rd. Synthesis and anti-cancer activity of some novel 5-azacytosine nucleosides. Nucleosides Nucleotides Nucleic Acids. 2003 Dec;22(12):2161-70. doi: 10.1081/ncn-120026872. PMID 14714764