Phase I Trial of Oral 5-Fluoro-2-Deoxycytidine With Oral Tetrahydrouridine in Patients With Advanced Solid Tumors

Inclusion Criteria

- INCLUSION CRITERIA:

- Patients must have histologically documented solid tumors whose disease has
progressed on standard therapy that is known to be associated with a survival
advantage or have disease for which there is no known standard therapy.

- Patients must have measurable or evaluable disease.

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

- Patients must have completed any chemotherapy, radiation therapy, biologic therapy,
or major surgery greater than or equal to 4 weeks prior to enrollment (6 weeks for
nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since
any prior administration of a study drug in a Phase 0 or equivalent study, at the
discretion of the Principal Investigator. Patients must have recovered to eligibility
levels from prior toxicity or adverse events. Patients with bone metastases or
hypercalcemia on IV bisphosphonate treatment prior to study entry may continue this
treatment.

- Age greater than or equal to18 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 or equal to 1.5 X institutional upper limit of
normal

- AST(SGOT)/ALT(SGPT) greater than or equal to 3 X institutional upper limit of
normal

- creatinine less than 1.5 X institutional upper limit of normal

OR

--creatinine clearance greater than or equal to 60 ML/min for patients with creatinine
levels

Above 1.5 X institutional upper limit of normal

- Because FdCyd has been shown to be teratogenic in animals, pregnant women are
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 childbearing potential must agree to either abstain from
sexual intercourse or use two forms of acceptable birth control, including one
barrier method, for 4 weeks prior to study entry, for the duration of study
participation, and for 3 months after completion of study. Men must use a latex
condom every time they have sexual intercourse during therapy and for 3 months after
study completion, even if they have had a successful vasectomy. 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.

- Ability to swallow liquids.

- Willingness to provide blood and urine samples for research purposes.

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, known HIV infection requiring protease inhibitor therapy, Hepatitis B,
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 brain metastases or carcinomatous meningitis are excluded from
this clinical trial, with the exception of patients whose brain metastatic disease
status has remained stable for greater than or equal to 2 months after treatment of
the brain metastases. Patients should be on stable doses of anti-seizure medications.
These patients may be enrolled at the discretion of the Principal Investigator.

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

- Malabsorption syndrome or other conditions that would interfere with intestinal
absorption.