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Aza-TdC in Treating Patients with Advanced or Refractory Solid Tumors

Trial Status: Active

This phase I trial studies the side effects and best dose of Aza-TdC in treating patients with solid tumors that have spread to other places in the body (advanced) and usually cannot be cured or controlled with treatment. Aza-TdC may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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 =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above 1.5 x 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, radiation therapy, 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 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 echocardiogram (ECHO) or multi-gated acquisition scan (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 human immunodeficiency virus (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 >= 1 month after treatment of the brain metastases; patients should not be on anti-seizure medications; these patients may be enrolled at the discretion of the principal investigator
  • Malabsorption syndrome or other conditions that would interfere with intestinal absorption


National Cancer Institute Developmental Therapeutics Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-411-1222
National Institutes of Health Clinical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-411-1222


I. To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral 5-aza-4’-thio-2’-deoxycytidine (Aza-TdC) administered daily for 5 days a week for 2 weeks, with one week off, in 21-day cycles, to patients with refractory solid tumors.


I. To determine the pharmacokinetics of oral Aza-TdC.

II. To document preliminary evidence of Aza-TdC activity.

III. To determine effect of study treatment on re-expression of select genes silenced by methylation in circulating tumor cells.

IV. To determine the effects of Aza-TdC on deoxyribonucleic acid (DNA) damage response (DDR) signaling and on genome-wide DNA methylation in tumor biopsy tissue.


I. To determine the effects of Aza-TdC on global ribonucleic acid (RNA) expression and on levels of DNMT1, DNMT3a, DNMT3b, and other select proteins in tumor biopsy tissue.

II. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with Aza-TdC response or resistance.

OUTLINE: This is a dose-escalation study.

Patients receive 5-aza-4’-thio-2’-deoxycytidine orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up between 27-30 days.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
James H. Doroshow

  • Primary ID 10114
  • Secondary IDs NCI-2017-01233, 18-C-0014
  • ID NCT03366116