Download 3.1 Eligibility Criteria • Patients must have histologically documented

PHI-70: CCRC: Phase I Trial of Oral 5-Fluoro-2-Deoxycytidine With Oral Tetrahydrouridine in Patients with Advanced
Solid Tumors (NCI#9127)
3.1 Eligibility 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 ≥ 4 weeks prior to enrollment (6 weeks for nitrosoureas or mitomycin C). Patients must
be ≥ 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 ≥ 18 years. Because no dosing or adverse event data are currently available on the use of
FdCyd and THU in patients < 18 years of age, children are excluded from this study, but may be
eligible for future pediatric Phase I combination trials.
•
Karnofsky performance status ≥ 60%, see Appendix A.
•
Life expectancy of greater than 3 months.
•
Patients must have normal organ and marrow function as defined below:
− absolute neutrophil count
≥ 1,500/mcL
− platelets
≥ 100,000/mcL
− total bilirubin
≤ 1.5 X institutional upper limit of normal
− AST(SGOT)/ALT(SGPT)
≤ 3 X institutional upper limit of normal
− creatinine
< 1.5 X institutional upper limit of normal
OR
− creatinine clearance
≥ 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 (Appendix J) must agree to either abstain from sexual intercourse or use
two forms of acceptable birth control, including one barrier method (Appendix J), 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.
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Ability to swallow liquids.
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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 biopsy (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 outlined in Section 9.
Protocol Version: 03/13/17
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PHI-70: CCRC: Phase I Trial of Oral 5-Fluoro-2-Deoxycytidine With Oral Tetrahydrouridine in Patients with Advanced
Solid Tumors (NCI#9127)
3.2 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
≥ 2 months after treatment of the brain metastases. Patients should be on stable doses of antiseizure 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.
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Malabsorption syndrome or other conditions that would interfere with intestinal absorption.
Protocol Version: 03/13/17
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