A Multi-Histology Phase II Study of 5-Fluoro-2-Deoxycytidine With Tetrahydrouridine (FdCyd + THU)
- 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 on several separate clinical trials.
- 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.
- Individuals 18 years of age and older who have advanced non-small cell lung cancer, breast cancer, bladder cancer, or head or neck cancer that has progressed after receiving standard treatment or for which no effective therapy exists.
- 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 each day 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.
Head and Neck Neoplasms
Urinary Bladder Neoplasms
Drug: 5-Fluoro-2-Deoxycytidine (FdCyd)
Drug: Tetrahydrouridine (THU)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Histology Phase II Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU)|
- Determine progression-free survival (PFS) and/or the response rate(CR + PR) of FdCyd [ Time Frame: 4 or 6 months ] [ Designated as safety issue: No ]
- Evaluate whether treatment with FdCyd and THU alters DNA methylation patterns in [ Time Frame: 2 Cycles ] [ Designated as safety issue: No ]
- Evaluate the safety and tolerability of FdCyd (100 mg/m2) + THU (350 mg/m2) [ Time Frame: 1 Cycle ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2009|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
FdCyd (100 mg/m2) + THU (350 mg/m2) administered 5 days/week for 2 weeks in 28-daycycles
Drug: 5-Fluoro-2-Deoxycytidine (FdCyd)
FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the AUC of the pare compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into DNA and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNM and in turn DNA methylation,can result in the re-expression of tumor suppressor genes.Drug: Tetrahydrouridine (THU)
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 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 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.
- Determine progression-free survival (PFS) and/or the response rate (CR + 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, and urothelial transitional cell carcinoma.
- Evaluate whether treatment with FdCyd and THU alters DNA methylation patterns in tumor biopsy samples before and during treatment by LINE-1 analysis.
- Evaluate the safety and tolerability of FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days per week for 2 weeks, in 28-day cycles, by intravenous infusion over 3 hours.
- Measure changes in the number of CTCs following treatment with FdCyd plus THU.
-Patients with histologically documented non-small cell lung cancer, head and neck cancer, urothelial transitional cell carcinoma, and breast carcinoma.
- This is a multicenter trial with NCI as the coordinating center and the California Cancer Consortium and UPMC as participating sites.
- FdCyd will be administered as an IV infusion over 3 hours with 20% of the daily dose of THU administered as an IV push and the remaining 80% co-administered with FdCyd by 3-hour infusion daily for 5 consecutive days of treatment per week for 2 consecutive weeks, followed by 2 weeks of no treatment, in a 28-day cycle.
- Blood and optional tumor biopsies for pharmacodynamic and pharmacokinetic studies will be obtained.
- The study will accrue a maximum of 185 patients including all centers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00978250
|Contact: Jennifer H Zlott||(301) firstname.lastname@example.org|
|Contact: James H Doroshow, M.D.||(301) email@example.com|
|United States, California|
|University of California, Davis||Recruiting|
|Davis, California, United States, 95616|
|City of Hope National Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|University of Southern California||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: James Doroshow, M.D. 301-496-4916 firstname.lastname@example.org|
|City of Hope Medical Group||Recruiting|
|South Pasadena, California, United States, 91030|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, Pennsylvania|
|Milton Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||James H Doroshow, M.D.||National Cancer Institute (NCI)|