A Multi-Histology Phase II Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 95
- Locations
- 4
- Primary Endpoint
- Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)
Study Overview
Brief Summary
Background:
- Two experimental drugs, FdCyd (also called 5-fluoro-2'-deoxcytidine), and THU (also called tetrahydrouridine), are undergoing trials to test their effectiveness in treating cancer that has not responded to standard therapies. FdCyd is thought to work by changing how genes work in cancer cells. THU does not have any anticancer effects on its own, but it helps keep the other drug, FdCyd, from being broken down by the body.
- These drugs are being tested in several separate clinical trials.
Objectives:
- To determine if FdCyd and THU can work together to control tumor growth.
- To evaluate the safety and tolerability of FdCyd and THU when given together.
Eligibility:
- Individuals 18 years of age and older who have advanced non-small cell lung cancer, breast cancer, bladder cancer, or head and neck cancer that has progressed after receiving standard treatment or for which no effective therapy exists.
Design:
- The drugs are given over 28-day periods called cycles. FdCyd and THU are given through a vein for about 3 hours each day on days 1, 5 and 8, 12 of each cycle.
- Clinical Center visits: FdCyd and THU will be given through a vein on days 1, 5 and 8, 12 of each cycle. During the Clinical Center visits, researchers will perform study tests and procedures to see how the study drugs are affecting the body.
- Patients will undergo a number of tests and procedures during the treatment cycle, including physical examinations, blood and urine samples for standard tests, imaging studies (ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scans) to evaluate tumor growth, and blood and urine samples to evaluate the amount of FdCyd and THU in the body and the body's response to the drugs.
- Patients may continue to receive FdCyd and THU if their cancer does not grow, if they do not have too many side effects, and if they are willing to do so.
Detailed Description
Background:
5-Fluoro-2'-deoxycytidine (FdCyd), a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, coadministration with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
Primary objective:
-Determine progression-free survival (PFS) and/or the response rate (Complete Response (CR) + Partial Response (PR)) of FdCyd administered 5 days per week for 2 weeks, in 28-day cycles, by intravenous infusion over 3 hours along with THU in patients with breast cancer, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial transitional cell carcinoma.
Exploratory objectives:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 120 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles
Intervention: 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU) (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)
Time Frame: until subject progressed or went off study for other reasons (up to approximately 1 year)
Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.
Progression-free Survival (PFS)
Time Frame: until subject progressed or went off study for other reasons (up to approximately 1 year)
Progression-free survival (PFS) is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new lesions.
Secondary Outcomes
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).(Date treatment consent signed to date off study, approximately 109 months and 16 days.)
Investigators
James Doroshow, M.D.
National Cancer Institute
National Cancer Institute (NCI)