Protocol Number: 09-C-0214

Title:

A Multi-Histology Phase II Study of 5-Fluoro-2'-Deoxycytidine with Tetrahydrouridine (FdCyd + THU)

Number:

09-C-0214

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 on 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 or 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 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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

-Patients must have histologically documented metastatic or unresectable non-small cell lung cancer, head and neck cancer, urothelial transitional cell carcinoma, or breast cancer whose disease has progressed after at least one line of standard therapy.

-Patients with solid tumors (non-small cell lung cancer, head and neck cancer, urothelial transitional cell carcinoma, and breast cancer) must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal 10 mm with spiral CT scan.

-Diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is enrolled prior to patient enrollment.

-Any prior therapy must have been completed greater than or equal to 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels from prior toxicity. Patients should be at least six weeks out from nitrosoureas and mitomycin C. Prior radiation should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study, and should have recovered to eligibility levels from any toxicities.

-Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of FdCyd and THU in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.

-Karnofsky performance status greater than or equal to 60%.

-Life expectancy of greater than 3 months.

-Patients must have normal organ and marrow function as defined below:

--absolute neutrophil count greater than or equal to 1,500/mcL

--platelets greater than or equal to 100,000/mcL

--total bilirubin less than 1.5 times institutional upper limit of normal

--AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal

--creatinine less than 1.5 times institutional upper limit of normal

OR

--creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above 1.5 times institutional upper limit of normal.

-Because FdCyd has been shown to be teratogenic in animals, pregnant women will be excluded from this trial. Nursing women are also excluded, as there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with FdCyd. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for 3 months after completion of study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she or her partner should inform the treating physician immediately.

-Ability to understand and the willingness to sign a written informed consent document.

-Patients should not be receiving any other investigational agents.

EXCLUSION CRITERIA:

-Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, immune deficiencies or confirmed diagnosis of HIV infection, Hepatitis B, Hepatitis C, or 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.

-History of allergic reactions attributed to fluoropyrimidines (e.g., capecitabine, fluorouracil, fluorodeoxyuridine) or tetrahydrouridine.

Special Instructions:

Currently Not Provided

Keywords:

DNA Methylation

Advanced Cancer

Methyltransferase Inhibitor

Epigenetics

Gene Re-Expression

Recruitment Keyword(s):

Breast Cancer

Head and Neck Cancer

Lung Cancer

Non-Small Cell Lung Cancer

Bladder Cancer

Condition(s):

Head and Neck Neoplasms

Lung Neoplasms

Urinary Bladder Neoplasms

Breast Neoplasms

Investigational Drug(s):

5-Fluoro-2-Deoxycytidine (FdCyd)

Investigational Device(s):

None

Intervention(s):

Drug: 5-Fluoro-2-Deoxycytidine (FdCyd)

Drug: Tetrahydrouridine (THU)

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Lapeyre JN, Becker FF. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun. 1979 Apr 13;8 (3):698-705.

Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003 Nov 20;34 (21):2042-54.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;5 (2):71-96. Epub 2008 Feb 20.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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