Imaging Study for FdCyd and THU Cancer Treatment

• To determine the safety of [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) administered intravenously with intravenous administration of 350 mg/m(2) of tetrahydrouridine (THU)
  

• To evaluate the pharmacokinetics of [F-18]-FdCyd via PET/CT
  

Drug: Tetrahydrouridine (THU)
N/A
Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
N/A

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.