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

Phase 0
18 Years
Open (Enrolling)
Head and Neck Neoplasms, Lung Neoplasms, Urinary Bladder Neoplasms, Breast Neoplasms

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Trial Information

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


- 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.


- 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.


- 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.


- 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.

Inclusion Criteria


- Enrolled in the NIH Phase II Clinical protocol evaluating FdCyd with THU (09-C-0214)
with target lesion measured as greater than or equal to 10mm with spiral CT scan.

- Written, voluntary, informed consent of the patient must be obtained in compliance
with institutional, state and federal guidelines

- For females: Negative serum pregnancy test OR post-menopausal for at least 2 years OR
patient has had a hysterectomy


- Participants with severe claustrophobia unresponsive to oral anxiolytics

- Subjects weighing > 400 lbs (weight limit for scanner table), or unable to fit
within the imaging gantry

- Known allergy to FdCyd

- The subject is unable to lie still for 75 minutes

- 5 Pregnant or lactating women. Pregnant women are excluded from this study because
the effects of 18F-FdCyd in pregnancy are not known. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to administration of
18FFdCyd in the mother, breastfeeding should be discontinued if the mother receives

- Participants with any co-existing medical or psychiatric condition that is likely to
interfere with study procedures and/or results

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

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)

Principal Investigator

Karen A Kurdziel, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institutes of Health Clinical Center (CC)


United States: Federal Government

Study ID:




Start Date:

October 2011

Completion Date:

October 2013

Related Keywords:

  • Head and Neck Neoplasms
  • Lung Neoplasms
  • Urinary Bladder Neoplasms
  • Breast Neoplasms
  • Imaging
  • Radiopharmaceutical
  • Safety
  • Dosimetry
  • Drug Distribution
  • Cancer
  • Urinary Bladder Neoplasms
  • Breast Neoplasms
  • Neoplasms
  • Head and Neck Neoplasms
  • Lung Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892