NCT01479348

Imaging Study for FdCyd and THU Cancer Treatment

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

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Background: \- The drugs FdCyd (also called 5-fluoro-2'-deoxycytidine) 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....

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 deoxyribonucleic acid (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, National Cancer Institute (NCI), Clinical Center, National Institutes of Health (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 positron emission tomography (PET)/computed tomography (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.

Conditions

• Head and Neck Neoplasms
• Lung Neoplasms
• Urinary Bladder Neoplasms
• Breast Neoplasms

Interventions

Type	Name	Description
DRUG	[F-18]-5-FLUORO-2'-DEOXYCYTIDINE	18FdCyd radiotracer
DRUG	Tetrahydrouridine intravenous (IV)	Total dose of THU = 350 mg/m\^2, IV
DRUG	Tetrahydrouridine (oral)	Total dose of THU is 3000 mg, oral
DIAGNOSTIC_TEST	Positron emission tomography (PET)/Computed tomography (CT)	One prior CT and 3 sequential whole body PET

Timeline

• Start date: 2011-11-01
• Primary completion: 2017-08-04
• Completion: 2019-01-11
• First posted: 2011-11-24
• Last updated: 2020-06-02
• Results posted: 2020-05-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study