Imaging Study for FdCyd and THU Cancer Treatment

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01479348
First received: November 22, 2011
Last updated: March 14, 2014
Last verified: June 2013
  Purpose

Background:

- The drugs FdCyd (also called 5-fluoro-2'-deoxcytidine) and THU (also called tetrahydrouridine) are being used in a cancer treatment study. Not a lot is known about how FdCyd works in the body. Researchers want to look at a modified form of FdCyd using imaging studies to see how the drug reacts with the cancer. This study is not a treatment study. It is open only to people who are already on the FdCyd and THU cancer treatment study.

Objectives:

- To study how FdCyd affects advanced cancer cells.

Eligibility:

- Participants in National Cancer Institute study 09-C-0214.

Design:

  • Participants will have two imaging studies, one before starting FdCyd and THU treatment and one after starting treatment.
  • Participants will have the modified FdCyd, known as F-18 FdCyd, with a dose of THU. The doses will be followed by two imaging study scans and frequent blood samples.
  • This procedure will be repeated at a later date, during the FdCyd and THU treatment period.
  • Treatment will not be provided as part of this study. This is an imaging study protocol only....

Condition Intervention Phase
Head and Neck Neoplasms
Lung Neoplasms
Urinary Bladder Neoplasms
Breast Neoplasms
Drug: Tetrahydrouridine (THU)
Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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)

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

Enrollment: 3
Study Start Date: October 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tetrahydrouridine (THU)
    N/A
    Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
    N/A
Detailed Description:

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 administration 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) or NCI Protocol #12-C-0066 (CTEP# 9127)) 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:

  • There are two arms to this study
  • The first arm will be patients enrolling in the therapeutic Phase II 5-FdCyd/THU study (NCI Protocol # 09-C-0214 (CTEP# 8351) in the NCI Developmental Therapeutics Clinic
  • The second arm will be patients enrolling in the Phase I 5-FdCyd/THU study (NCI Protocol #12-C-0066 (CTEP# 9127)) in the NCI Developmental Therapeutics Clinic.
  • Patients will undergo an initial [F-18]-FdCyd + THU PET/CT imaging prior to therapeutic dosing on study NCI Protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol #12-C-0066 (CTEP# 9127). Repeat imaging will be performed while the patient is receiving FdCyd + THU therapy under the parent therapeutic protocol. This imaging must be completed 2-5 days after cycle start and at least 2 hours after a dose. Upon completion of repeat imaging, patients will be taken off this imaging study 24 hours after the last imaging session.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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

EXCLUSION CRITERIA:

  • 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 18FFdCyd
  • Participants with any co-existing medical or psychiatric condition that is likely to interfere with study procedures and/or results
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01479348

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Karen A Kurdziel, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01479348     History of Changes
Other Study ID Numbers: 120014, 12-C-0014
Study First Received: November 22, 2011
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Imaging
Radiopharmaceutical
Safety
Dosimetry
Drug Distribution
Cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Breast Neoplasms
Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Tetrahydrouridine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014