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| ID | Type | Description | Link |
|---|---|---|---|
| 12-C-0014 |
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Slow, insufficient accrual.
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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:
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.
biodistribution and safety of the radiolabeled form.
OBJECTIVES:
ELIGIBILITY:
DESIGN:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1/Intravenous (IV) Tetrahydrouridine (THU) | Experimental | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine |
|
| 2/Oral Tetrahydrouridine (THU) | Experimental | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [F-18]-5-FLUORO-2'-DEOXYCYTIDINE | Drug | 18FdCyd radiotracer |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 9 minutes, 32 minutes, 56 minutes and 2 hours after injection |
| Number of Participants With Serious and Non-Serious Adverse Events |
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EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Karen A Kurdziel, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1255749 | Background | 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. | |
| 2407810 | Background | 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. |
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No participants were enrolled in the 2/Oral Tetrahydrouridine (THU) Group.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1/Intravenous (IV) Tetrahydrouridine (THU) | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine [F-18]-5-FLUORO-2'-DEOXYCYTIDINE: 18FdCyd radiotracer Tetrahydrouridine intravenous (IV): Total dose of THU = 350 mg/m^2, IV Tetrahydrouridine (oral): Total dose of THU is 3000 mg, oral Positron emission tomography (PET)/Computed tomography (CT): One prior CT and 3 sequential whole body PET |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 9, 2015 |
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| Tetrahydrouridine intravenous (IV) | Drug | Total dose of THU = 350 mg/m^2, IV |
|
|
| Tetrahydrouridine (oral) | Drug | Total dose of THU is 3000 mg, oral |
|
|
| Positron emission tomography (PET)/Computed tomography (CT) | Diagnostic Test | One prior CT and 3 sequential whole body PET |
|
|
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. |
| Date treatment consent signed to date off study, approximately 20 months and 12 days. |
| 14116219 | Background | 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. |
| FG001 | 2/Oral Tetrahydrouridine (THU) | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine [F-18]-5-FLUORO-2'-DEOXYCYTIDINE: 18FdCyd radiotracer Tetrahydrouridine intravenous (IV): Total dose of THU = 350 mg/m^2, IV Tetrahydrouridine (oral): Total dose of THU is 3000 mg, oral Positron emission tomography (PET)/Computed tomography (CT): One prior CT and 3 sequential whole body PET |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1/Intravenous (IV) Tetrahydrouridine (THU) | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine [F-18]-5-FLUORO-2'-DEOXYCYTIDINE: 18FdCyd radiotracer Tetrahydrouridine intravenous (IV): Total dose of Tetrahydrouridine (THU) = 350 mg/m^2, IV Tetrahydrouridine (oral): Total dose of THU is 3000 mg, oral Positron emission tomography (PET)/Computed tomography (CT): One prior CT and 3 sequential whole body PET |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
| |||||||||||||||||||||||
| Baseline Tumor Types | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | adverse events | Within 5 days after interventions |
|
|
| |||||||||||||||||||||||||||||||||||||
| Primary | 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. | Posted | Mean | Standard Deviation | mSv/MBq | 1 year |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | One participant contributed to data in each row. | Posted | Number | TBR ratio | 9 minutes, 32 minutes, 56 minutes and 2 hours after injection |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | Date treatment consent signed to date off study, approximately 20 months and 12 days. |
|
|
Date treatment consent signed to date off study, approximately 20 months and 12 days.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1/Intravenous (IV) Tetrahydrouridine (THU) | [F-18]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine [F-18]-5-FLUORO-2'-DEOXYCYTIDINE: 18FdCyd radiotracer Tetrahydrouridine intravenous (IV): Total dose of Tetrahydrouridine (THU) = 350 mg/m^2, IV Tetrahydrouridine (oral): Total dose of THU is 3000 mg, oral Positron emission tomography (PET)/Computed tomography (CT): One prior CT and 3 sequential whole body PET | 2 | 5 | 2 | 5 | 2 | 5 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death NOS | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Karen Kurdziel | National Cancer Institute | 804-897-1207 | kurdziek@nih.gov |
| Apr 13, 2020 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: IV FdCyd + THU | Mar 18, 2015 | Apr 13, 2020 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Oral FdCyd + THU | Mar 18, 2015 | Apr 13, 2020 | ICF_002.pdf |
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D008175 | Lung Neoplasms |
| D001749 | Urinary Bladder Neoplasms |
| D001943 | Breast Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D013767 | Tetrahydrouridine |
| D049268 | Positron-Emission Tomography |
| D000072078 | Positron Emission Tomography Computed Tomography |
| ID | Term |
|---|---|
| D014529 | Uridine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |
| D014057 | Tomography, X-Ray Computed |
| D064847 | Multimodal Imaging |
| D011856 | Radiographic Image Enhancement |
| D011859 | Radiography |
| D014056 | Tomography, X-Ray |
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Hepatocellular Carcinoma |
|
| Title | Measurements |
|---|---|
|
| Day 3 Adverse Events |
|
| Day 4 Adverse Events |
|
| Day 5 Adverse Events |
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