About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

absolute neutrophil count >= 1,500/mcL

Disqualifiers

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.

Evaluable or measurable disease outside the CNS

Trial design

Design model

Single group

Treatments tested in this trial

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.

Treatment groups

75 Participants

are divided into 1 treatment group

Group A: 1Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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

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

Time frame

Cycle 1 and Cycle 2

Secondary outcomes

1

To determine the pharmacokinetics of oral aza-TdCyd

To determine the pharmacokinetics of oral aza-TdC

Time frame

Cycle 1

2

To document preliminary evidence of aza-TdCyd activity

To document preliminary evidence of aza-TdC activity

Time frame

Cycle 1 and 2

3

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

4

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

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

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts