RECRUITING

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

Conditions

Neoplasms Solid Tumors Pharmacodynamics DNA Methylation Pharmacokinetics Nucleoside Analog Epigenetics

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

Phase I Trial of 5-aza-4'-Thio-2'-Deoxycytidine (Aza-TdC) in Patients With Advanced Solid Tumors

Quick Facts

Study Start:2018-11-05

Study Completion:2026-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03366116

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 * AST(SGOT)/ALT(SGPT) \<=5 X institutional upper limit of normal for patients with liver metastases * creatinine \<=1.5X institutional upper limit of normal * 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.	* 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.

Inclusion Criteria

Exclusion 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
* AST(SGOT)/ALT(SGPT) \<=5 X institutional upper limit of normal for patients with liver metastases
* creatinine \<=1.5X institutional upper limit of normal
* 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.

* 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.

Contacts and Locations

Study Contact

DTC Referral Coordinators

CONTACT

(240) 781-3400

dtcreferralcoordinators@nih.gov

James H Doroshow, M.D.

CONTACT

(240) 781-3320

doroshoj@mail.nih.gov

Principal Investigator

James H Doroshow, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

James H Doroshow, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-11-05

Study Completion Date2026-09-30

Study Record Updates

Study Start Date2018-11-05

Study Completion Date2026-09-30

Terms related to this study

Keywords Provided by Researchers

Pharmacodynamics
DNA Methylation
Pharmacokinetics
Nucleoside Analog
Epigenetics

Additional Relevant MeSH Terms

Neoplasms
Solid Tumors