Imaging Study for FdCyd and THU Cancer Treatment
| Status: | Terminated |
|---|---|
| Conditions: | Breast Cancer, Lung Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 1/17/2019 |
| Start Date: | November 1, 2011 |
| End Date: | January 11, 2019 |
Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine
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....
- 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....
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.
- 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.
- 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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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