Trial Information

Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine

BACKGROUND:

- In pre-clinical models, 5-fluoro-2'-deoxycytidine (FdCyd), administered along with

tetrahydrouridine (THU; an inhibitor of cytidine/deoxycytidine deaminase), has shown
superior anti-tumor activity as compared with 5-fluorouracil.

- FdCyd can be phosphorylated to 5-fluoro-2'-deoxycytidylate (FdCMP) by deoxycytidine

kinase and the nucleotide deaminated to FdUMP by deoxycytidylate (dCMP) deaminase.

The activity of dCMP deaminase is reported to be higher in human malignancies than in normal
tissues, which may result in selective cytotoxicity.

- FdCyd is an inhibitor of DNA methyltransferase and DNA methylation, resulting in
reexpression of genes silenced by DNA hypermethylation. It is being evaluated in a
phase II multihistology clinical trial at the Developmental Therapeutics Clinic, NCI,
Clinical Center, NIH.

- While FdCyd + THU has shown preliminary evidence of activity in early phase trials not
all patients show clinical response. The establishment of a radiolabeled form to image
the biodistribution in vivo at baseline and during therapy may provide insight into the
distribution of the therapeutic drug.

- The first step in the development of such an in vivo marker is to determine the

biodistribution and safety of the radiolabeled form.

OBJECTIVES:

- Determine the safety of [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) administered
intravenously with intravenous administration of 350 mg/m2 of tetrahydrouridine (THU).

- Estimate the radiation dosimetry of [F-18]-FdCyd in humans.

ELIGIBILITY:

- Only patients enrolled in NCI Phase II Study evaluating FdCyd with THU (NCI Protocol #
09-C-0214 (CTEP# 8351)) at the NIH Clinical Center will be eligible to participate in
this study).

- Patients must have a target lesion greater than or equal to 10mm

- May not be pregnant or lactating; must be less than or equal to 350 lbs; and may not
have known allergy to FdCyd or contraindications to PET/CT imaging.

DESIGN:

- Patients enrolling in the therapeutic Phase II 5-FdCyd/THU study (NCI Protocol # 09-C-
0214 (CTEP# 8351)) in the NCI Developmental Therapeutics Clinic who also meet the
inclusion criteria of this protocol will be invited to participate.

- Patients will undergo baseline [F-18]-FdCyd + THU PET/CT imaging prior to therapeutic
dosing on study NCI Protocol # 09-C-0214 (CTEP# 8351). Repeat imaging will be performed
while the patient is receiving FdCyd + THU therapy under the parent therapeutic
protocol. This imaging must be completed within 2-weeks of the baseline PET/CT. Upon
completion of repeat imaging, patients will be taken off this imaging study.