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Head and Neck NeoplasmsEarly Phase 1NCT01479348

Imaging Study for FdCyd and THU Cancer Treatment

A Early Phase 1 study testing [F-18]-5-FLUORO-2'-DEOXYCYTIDINE, Tetrahydrouridine intravenous (IV) and Tetrahydrouridine (oral) in people with Head and Neck Neoplasms and Lung Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
[F-18]-5-FLUORO-2'-DEOXYCYTIDINE, Tetrahydrouridine intravenous (IV) and Tetrahydrouridine (oral)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
1 Nov 2011to 11 Jan 2019
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Enrolled in the National Institutes of Health (NIH) Phase II Clinical protocol evaluating 5-fluro-2'-deoxycytidine (FdCyd) with Tetrahydrouridine (THU) (09-C-0214) with target lesion measured as greater than or equal to 10mm with spiral computed tomography (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

Who cannot join

  • 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 18F-FdCyd in the mother, breastfeeding should be discontinued if the mother receives 18F-FdCyd
  • Participants with any co-existing medical or psychiatric condition that is likely to interfere with study procedures and/or results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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.
Read more

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....
Read the 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.
Being tested
[F-18]-5-FLUORO-2'-DEOXYCYTIDINE, Tetrahydrouridine intravenous (IV), Tetrahydrouridine (oral), Positron emission tomography (PET)/Computed tomography (CT)
Keywords
Imaging, Radiopharmaceutical, Safety, Dosimetry, Drug Distribution, Cancer
Medical subject headings
Head and Neck Neoplasms, Lung Neoplasms, Urinary Bladder Neoplasms, Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [F-18]-5-FLUORO-2'-DEOXYCYTIDINEDrug

    Also called 18FdCyd

    18FdCyd radiotracer

  • Tetrahydrouridine intravenous (IV)Drug

    Also called THU

    Total dose of THU = 350 mg/m^2, IV

  • Tetrahydrouridine (oral)Drug

    Also called THU

    Total dose of THU is 3000 mg, oral

  • Positron emission tomography (PET)/Computed tomography (CT)Diagnostic test

    Also called PET scan/CT scan

    One prior CT and 3 sequential whole body PET

Study groups in NCT01479348
Study groupRoleWhat they receive
1/Intravenous (IV) Tetrahydrouridine (THU)Experimental[F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine
Receives: Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE; Drug: Tetrahydrouridine intravenous (IV); Drug: Tetrahydrouridine (oral); Diagnostic Test: Positron emission tomography (PET)/Computed tomography (CT)
2/Oral Tetrahydrouridine (THU)Experimental[F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine
Receives: Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE; Drug: Tetrahydrouridine intravenous (IV); Drug: Tetrahydrouridine (oral); Diagnostic Test: Positron emission tomography (PET)/Computed tomography (CT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

    [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) was administered intravenously with administration of tetrahydrouridine (THU) and the frequency and severity of adverse events was observed. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 0 is normal, Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event.

    Measured: Within 5 days after interventions

  2. Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans

    Radiation dosimetry was determined based on the first patients. This involved making region of interest measurements on the scan for each major organ and measuring the uptake. Using standard dosimetry software this is converted into mSv/MBq, a standard measure of dosimetry. The software is known as Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA) and is commonly used to generate this kind of data.

    Measured: 1 year

Secondary outcomes (2)

  1. Tumor to Background Ratios (TBRs) of Target Lesions at 4 Time Points After Injection

    Participants were scanned by positron emission tomography (PET) and lesions were measured at 4 time points after injection.

    Measured: 9 minutes, 32 minutes, 56 minutes and 2 hours after injection

  2. Number of Participants With Serious and Non-Serious Adverse Events

    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Measured: Date treatment consent signed to date off study, approximately 20 months and 12 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2011 (estimated)
  2. Study start1 Nov 2011
  3. Primary completion4 Aug 2017
  4. Study completion11 Jan 2019

Why it stopped: Slow, insufficient accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01479348
Sponsor's protocol ID
120014
Other IDs
12-C-0014
Status last verified
May 2020
First submitted
22 Nov 2011
Last updated
2 Jun 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Carter SK. Editorial: Large-bowel cancer-The current status of treatment. J Natl Cancer Inst. 1976 Jan;56(1):3-10. doi: 10.1093/jnci/56.1.3. No abstract available.

    PubMed 1255749

  • Doroshow JH, Multhauf P, Leong L, Margolin K, Litchfield T, Akman S, Carr B, Bertrand M, Goldberg D, Blayney D, et al. Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol. 1990 Mar;8(3):491-501. doi: 10.1200/JCO.1990.8.3.491.

    PubMed 2407810

  • HARTMANN JR, ORIGENES ML Jr, MURPHY ML, SITARZ A, ERLANDSON M. EFFECTS OF 2'-DEOXY-5-FLUOROURIDINE (NSC-27640) AND 5-FLUOROURACIL (NSC-19893) ON CHILDHOOD LEUKEMIA. Cancer Chemother Rep. 1964 Jan;34:51-4. No abstract available.

    PubMed 14116219

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing [F-18]-5-FLUORO-2'-DEOXYCYTIDINE, Tetrahydrouridine intravenous (IV) and Tetrahydrouridine (oral) in people with Head and Neck Neoplasms and Lung Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (time frame: Within 5 days after interventions). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01479348, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2020; AzTrials last refreshed its copy on 2 Nov 2026.

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