NCT01479348

Brief 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....

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for early_phase_1

Timeline
Completed

Started Nov 2011

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2011

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

November 22, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 24, 2011

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 4, 2017

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 11, 2019

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

May 22, 2020

Completed
Last Updated

June 2, 2020

Status Verified

May 1, 2020

Enrollment Period

5.8 years

First QC Date

November 22, 2011

Results QC Date

April 27, 2020

Last Update Submit

May 21, 2020

Conditions

Keywords

ImagingRadiopharmaceuticalSafetyDosimetryDrug DistributionCancer

Outcome Measures

Primary Outcomes (2)

  • 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.

    Within 5 days after interventions

  • 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.

    1 year

Secondary Outcomes (2)

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

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

  • Number of Participants With Serious and Non-Serious Adverse Events

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

Study Arms (2)

1/Intravenous (IV) Tetrahydrouridine (THU)

EXPERIMENTAL

\[F-18\]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine

Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINEDrug: 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

Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINEDrug: Tetrahydrouridine intravenous (IV)Drug: Tetrahydrouridine (oral)Diagnostic Test: Positron emission tomography (PET)/Computed tomography (CT)

Interventions

18FdCyd radiotracer

Also known as: 18FdCyd
1/Intravenous (IV) Tetrahydrouridine (THU)2/Oral Tetrahydrouridine (THU)

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

Also known as: THU
1/Intravenous (IV) Tetrahydrouridine (THU)2/Oral Tetrahydrouridine (THU)

Total dose of THU is 3000 mg, oral

Also known as: THU
1/Intravenous (IV) Tetrahydrouridine (THU)2/Oral Tetrahydrouridine (THU)

One prior CT and 3 sequential whole body PET

Also known as: PET scan/CT scan
1/Intravenous (IV) Tetrahydrouridine (THU)2/Oral Tetrahydrouridine (THU)

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • 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.

    PMID: 1255749BACKGROUND
  • 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.

    PMID: 2407810BACKGROUND
  • 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.

    PMID: 14116219BACKGROUND

MeSH Terms

Conditions

Head and Neck NeoplasmsLung NeoplasmsUrinary Bladder NeoplasmsBreast NeoplasmsNeoplasms

Interventions

TetrahydrouridinePositron-Emission TomographyPositron Emission Tomography Computed Tomography

Condition Hierarchy (Ancestors)

Neoplasms by SiteRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

UridinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesTomography, Emission-ComputedImage Interpretation, Computer-AssistedDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisImage EnhancementPhotographyRadionuclide ImagingTomographyDiagnostic Techniques, RadioisotopeTomography, X-Ray ComputedMultimodal ImagingRadiographic Image EnhancementRadiographyTomography, X-Ray

Results Point of Contact

Title
Dr. Karen Kurdziel
Organization
National Cancer Institute

Study Officials

  • Karen A Kurdziel, M.D.

    National Cancer Institute (NCI)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 22, 2011

First Posted

November 24, 2011

Study Start

November 1, 2011

Primary Completion

August 4, 2017

Study Completion

January 11, 2019

Last Updated

June 2, 2020

Results First Posted

May 22, 2020

Record last verified: 2020-05

Data Sharing

IPD Sharing
Will not share

Locations