Imaging Study for FdCyd and THU Cancer Treatment
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| ClinicalTrials.gov Identifier: NCT01479348 |
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Recruitment Status :
Completed
First Posted : November 24, 2011
Last Update Posted : July 6, 2018
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Sponsor:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Head and Neck Neoplasms Lung Neoplasms Urinary Bladder Neoplasms Breast Neoplasms | Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE Drug: Tetrahydrouridine (IV) Drug: Tetrahydrouridine (oral) Diagnostic Test: PET/CT | Early Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 5 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Diagnostic |
| Official Title: | Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine |
| Study Start Date : | November 1, 2011 |
| Actual Primary Completion Date : | August 4, 2017 |
| Actual Study Completion Date : | August 4, 2017 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: 1/IV THU
[F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine
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Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
18FdCyd radiotracer Drug: Tetrahydrouridine (IV) Total dose of THU = 350 mg/m2, IV Drug: Tetrahydrouridine (oral) Total dose of THU is 3000 mg, oral Diagnostic Test: PET/CT One prior CT and 3 sequential whole body PET |
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Experimental: 2/Oral THU
[F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine
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Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
18FdCyd radiotracer Drug: Tetrahydrouridine (IV) Total dose of THU = 350 mg/m2, IV Drug: Tetrahydrouridine (oral) Total dose of THU is 3000 mg, oral Diagnostic Test: PET/CT One prior CT and 3 sequential whole body PET |
Primary Outcome Measures :
- Safety of [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) administered intravenously with administration of tetrahydrouridine (THU) [ Time Frame: Within 5 days after interventions ]List of adverse event frequency
- Estimate the radiation dosimetry of [F-18]-FdCyd in humans [ Time Frame: 1 year ]Radiation dosimetry
Secondary Outcome Measures :
- To evaluate the pharmacokinetics of [F-18]- FdCyd via PET/CT [ Time Frame: Completion of study ]Drug level in the blood
- To evaluate the distribution of FdCyd in tumorous and nontumoroustissue [ Time Frame: Completion of study ]Distribution of FdCyd in tumorous and non-tumorous tissue
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479348
Locations
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | |
| Bethesda, Maryland, United States, 20892 | |
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Karen A Kurdziel, M.D. | National Cancer Institute (NCI) |
Additional Information:
Publications:
| ClinicalTrials.gov Identifier: | NCT01479348 History of Changes |
| Other Study ID Numbers: |
120014 12-C-0014 |
| First Posted: | November 24, 2011 Key Record Dates |
| Last Update Posted: | July 6, 2018 |
| Last Verified: | February 13, 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
Keywords provided by National Institutes of Health Clinical Center (CC):
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Imaging Radiopharmaceutical Safety |
Dosimetry Drug Distribution Cancer |
Additional relevant MeSH terms:
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Neoplasms Breast Neoplasms Lung Neoplasms Head and Neck Neoplasms Urinary Bladder Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Respiratory Tract Neoplasms Thoracic Neoplasms |
Lung Diseases Respiratory Tract Diseases Urologic Neoplasms Urogenital Neoplasms Urinary Bladder Diseases Urologic Diseases Tetrahydrouridine Antimetabolites Molecular Mechanisms of Pharmacological Action |