"Can experimental medicine change how genes work in cancer cells?"
18 to 100 years old
Drug study, Phase 1
The purpose of this study is to test the safety of experimental medicine, FdCyd, (also called 5-fluoro-2’-deoxycytidine) and experimental medicine,THU, (also called tetrahydrouridine), and find out the dose of the drugs that can be safely given to humans. We are trying to understand how FdCyd and THU work in humans, how your body handles these drugs, what side effects the drugs cause, and the safety of the drugs at the given dose. 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 your body.
This study requires
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Who can participate?
- 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 countgreater than or equal to 1,500/mcL
- plateletsgreater than or equal to 100,000/mcL
- total bilirubinless 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
- creatinineless than 1.5 X institutional upper limit of normal
--creatinine clearancegreater 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, and biopsy samples if on the expansion phase of the study, for research purposes. For the expansion cohort, patients must have tumor amenable to biospy (excisional or incision biopsies of skin or H & N lesions under visualization) and willingness to undergo a tumor biopsy or patient will be undergoing a procedure due to medical necessity during which the tissue may be collected, or tumor biopsy tissue from a previous research study or medical care is available for submission at registration. Criteria for the submission of tissue are:
- Tissue must have been collected within 3 months prior to registration
- Patient has not received any intervening therapy for their cancer since the collection of the tumor sample
- Tumor tissue must meet the minimum requirements
- 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.