Imaging Study for FdCyd and THU Cancer Treatment
关键词
抽象
描述
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.
日期
| 最后验证: | 04/30/2020 |
| 首次提交: | 11/21/2011 |
| 提交的预估入学人数: | 11/21/2011 |
| 首次发布: | 11/23/2011 |
| 上次提交的更新: | 05/20/2020 |
| 最近更新发布: | 06/01/2020 |
| 首次提交结果的日期: | 04/26/2020 |
| 首次提交质量检查结果的日期: | 05/05/2020 |
| 首次发布结果的日期: | 05/21/2020 |
| 实际学习开始日期: | 10/31/2011 |
| 预计主要完成日期: | 08/03/2017 |
| 预计完成日期: | 01/10/2019 |
状况或疾病
干预/治疗
Drug: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE
Drug: Tetrahydrouridine intravenous (IV)
Drug: Tetrahydrouridine (oral)
Diagnostic Test: Positron emission tomography (PET)/Computed tomography (CT)
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: 1/Intravenous (IV) Tetrahydrouridine (THU) [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine | |
| Experimental: 2/Oral Tetrahydrouridine (THU) [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | - INCLUSION CRITERIA: - 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 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 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 |
结果
主要结果指标
1. Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [Within 5 days after interventions]
2. Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans [1 year]
次要成果指标
1. 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]
2. Number of Participants With Serious and Non-Serious Adverse Events [Date treatment consent signed to date off study, approximately 20 months and 12 days.]
