A Multi-Histology Phase II Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU)

• ClinicalTrials.gov Identifier: NCT00978250
• Recruitment Status: Completed
• First Posted: September 16, 2009
• Results First Posted: December 27, 2019
• Last Update Posted: December 27, 2019
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): James Doroshow, M.D., National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Head and Neck Neoplasms; Lung Neoplasms; Urinary Bladder Neoplasms; Breast Neoplasms
• Intervention: Drug: 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
• Enrollment: 95

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Non-Small Cell Lung Cancer Stratum	Breast Cancer Stratum	Bladder Cancer Stratum	Head and Neck Cancer Stratum
Arm/Group Description	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles.
Period Title: Overall Study
Started	25	30	18	22
Completed	25	29	18	21
Not Completed	0	1	0	1
Reason Not Completed
Late determination of ineligibility	0	1	0	1

Baseline Characteristics

Arm/Group Title		Non-Small Cell Lung Cancer Stratum	Breast Cancer Stratum	Bladder Cancer Stratum	Head and Neck Cancer Stratum	Total
Arm/Group Description		FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation,can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation,can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation,can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation,can result in the re-expression of tumor suppressor genes.	Total of all reporting groups
Overall Number of Baseline Participants		25	30	18	22	95
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	17 68.0%	24 80.0%	4 22.2%	16 72.7%	61 64.2%
	>=65 years	8 32.0%	6 20.0%	14 77.8%	6 27.3%	34 35.8%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
		59.92 (9.95)	56.04 (10.07)	67.77 (8.93)	55.17 (11.70)	59.08 (11.08)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
	Female	9 36.0%	30 100.0%	3 16.7%	3 13.6%	45 47.4%
	Male	16 64.0%	0 0.0%	15 83.3%	19 86.4%	50 52.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
	Hispanic or Latino	0 0.0%	10 33.3%	1 5.6%	2 9.1%	13 13.7%
	Not Hispanic or Latino	25 100.0%	20 66.7%	17 94.4%	20 90.9%	82 86.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	6 24.0%	3 10.0%	3 16.7%	3 13.6%	15 15.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 12.0%	4 13.3%	0 0.0%	2 9.1%	9 9.5%
	White	16 64.0%	22 73.3%	15 83.3%	17 77.3%	70 73.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	1 3.3%	0 0.0%	0 0.0%	1 1.1%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	25 participants	30 participants	18 participants	22 participants	95 participants
		25 100.0%	30 100.0%	18 100.0%	22 100.0%	95 100.0%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival (PFS) is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	until subject progressed or went off study for other reasons (up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

All 93 patients eligible for the study were assessed for PFS, including patients with advanced non-small cell lung cancer, breast cancer, bladder cancer, or head and neck cancer. Two patients were determined ineligible for the study and never received study drug.

Arm/Group Title	Non-Small Cell Cancer Stratum	Breast Cancer Stratum	Bladder Cancer Stratum	Heand and Neck Cancer Stratum
Arm/Group Description:	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of daunomycin DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of daunomycin DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of daunomycin DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of daunomycin DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
Overall Number of Participants Analyzed	25	29	18	21
Median (95% Confidence Interval); Unit of Measure: months
	2.3; (1.6 to 3.9)	3.7; (1.8 to 5.3)	3.6; (1.7 to 8.0)	1.7; (1.7 to 4.5)

2. Primary Outcome

Title	Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)
Description	Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.
Time Frame	until subject progressed or went off study for other reasons (up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

All 93 patients eligible for the study were assessed for complete response (CR) or partial response (PR), including patients with advanced non-small cell lung cancer, breast cancer, bladder cancer, or head and neck cancer. Two patients were determined ineligible for the study and never received study drug.

Arm/Group Title	Non-Small Cell Cancer Stratum	Breast Cancer Stratum	Bladder Cancer Stratum	Head and Neck Cancer Stratum
Arm/Group Description:	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
Overall Number of Participants Analyzed	25	29	18	21
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0.0; (0.0 to 13.7)	6.9; (0.8 to 22.8)	5.6; (0.1 to 27.3)	0.0; (0.0 to 16.1)

3. Secondary Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).
Description	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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.
Time Frame	Date treatment consent signed to date off study, approximately 109 months and 16 days.

Outcome Measure Data

Analysis Population Description

Two patients were determined ineligible for the study and never received study drug. Adverse Events are not being reported by stratum because this was not specified in the protocol.

Arm/Group Title	5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
Arm/Group Description:	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
Overall Number of Participants Analyzed	93
Measure Type: Count of Participants; Unit of Measure: Participants
	91 97.8%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 109 months and 16 days. Two patients were determined ineligible for the study and never received study drug.
Adverse Event Reporting Description	Adverse Events are not being reported by stratum because this was not specified in the protocol.
Arm/Group Title	5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
Arm/Group Description	FdCyd (100 mg/m(2)) + THU (350 mg/m(2)) administered 5 days/week for 2 weeks in 28-day cycles 5-Fluoro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU): FdCyd, a fluoropyrimidine nucleoside analog, has a short (10-minute) half-life and is rapidly degraded in vivo by cytidine deaminase. However, co-administration with THU, an inhibitor of cytidine/deoxycytidine deaminase, has been shown to increase the area under the curve (AUC) of the parent compound more than 4-fold. Increased FdCyd exposure allows it to be taken up intracellularly and converted to its triphosphate, which is incorporated into deoxyribonucleic acid (DNA) and inhibits the action of the enzyme DNA methyltransferase (DNMT). Inhibition of DNMT, and in turn DNA methylation, can result in the re-expression of tumor suppressor genes.
All-Cause Mortality
	5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
	Affected / at Risk (%)
Total	8/93 (8.60%)
Serious Adverse Events
	5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
	Affected / at Risk (%)	# Events
Total	38/93 (40.86%)
Blood and lymphatic system disorders
Anemia † 1	4/93 (4.30%)	5
Febrile neutropenia † 1	1/93 (1.08%)	1
Cardiac disorders
Atrial fibrillation † 1	1/93 (1.08%)	1
Cardiac arrest † 1	1/93 (1.08%)	1
Eye disorders
Retinopathy † 1	1/93 (1.08%)	1
Gastrointestinal disorders
Abdominal distension † 1	1/93 (1.08%)	1
Abdominal pain † 1	6/93 (6.45%)	7
Colitis † 1	1/93 (1.08%)	1
Constipation † 1	1/93 (1.08%)	1
Diarrhea † 1	4/93 (4.30%)	6
Duodenal ulcer † 1	1/93 (1.08%)	1
Dysphagia † 1	4/93 (4.30%)	4
Esophagitis † 1	1/93 (1.08%)	1
Gastrointestinal disorders - Other, Diverticulitis † 1	1/93 (1.08%)	1
Ileus † 1	1/93 (1.08%)	1
Mucositis oral † 1	2/93 (2.15%)	2
Nausea † 1	3/93 (3.23%)	4
Oral hemorrhage † 1	1/93 (1.08%)	1
Vomiting † 1	4/93 (4.30%)	5
Gastrointestinal disorders - Other, Pyloric ulcer † 1	1/93 (1.08%)	1
Gastrointestinal disorders - Other, Partial small bowel obstruction † 1	1/93 (1.08%)	1
General disorders
Death NOS † 1	3/93 (3.23%)	3
Fatigue † 1	5/93 (5.38%)	5
Fever † 1	3/93 (3.23%)	3
Multi-organ failure † 1	1/93 (1.08%)	1
Infections and infestations
Enterocolitis infectious † 1	1/93 (1.08%)	1
Infections and infestations - Other, port infection (right) † 1	1/93 (1.08%)	1
Lung infection † 1	3/93 (3.23%)	3
Mucosal infection † 1	1/93 (1.08%)	1
Sepsis † 1	1/93 (1.08%)	1
Upper respiratory infection † 1	1/93 (1.08%)	1
Urinary tract infection † 1	2/93 (2.15%)	2
Infections and infestations - Other, Clostridium difficile † 1	1/93 (1.08%)	1
Infections and infestations - Other, Viral syndrome † 1	1/93 (1.08%)	1
Injury, poisoning and procedural complications
Vascular access complication † 1	1/93 (1.08%)	1
Investigations
Alkaline phosphatase increased † 1	1/93 (1.08%)	1
Lymphocyte count decreased † 1	6/93 (6.45%)	6
Neutrophil count decreased † 1	4/93 (4.30%)	6
Platelet count decreased † 1	3/93 (3.23%)	6
Weight loss † 1	1/93 (1.08%)	1
White blood cell decreased † 1	5/93 (5.38%)	6
Metabolism and nutrition disorders
Anorexia † 1	2/93 (2.15%)	3
Dehydration † 1	3/93 (3.23%)	4
Hypercalcemia † 1	3/93 (3.23%)	4
Hypermagnesemia † 1	1/93 (1.08%)	1
Hypoalbuminemia † 1	1/93 (1.08%)	1
Hypokalemia † 1	3/93 (3.23%)	3
Hyponatremia † 1	1/93 (1.08%)	1
Hypophosphatemia † 1	2/93 (2.15%)	3
Musculoskeletal and connective tissue disorders
Back pain † 1	1/93 (1.08%)	1
Generalized muscle weakness † 1	2/93 (2.15%)	2
Myalgia † 1	1/93 (1.08%)	1
Non-cardiac chest pain † 1	1/93 (1.08%)	1
Pain in extremity † 1	1/93 (1.08%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1 [1]	3/93 (3.23%)	3
Tumor pain † 1	1/93 (1.08%)	1
Nervous system disorders
Cognitive disturbance † 1	1/93 (1.08%)	1
Nervous system disorders - Other, Bilateral lower extremity weakness/paraplegia † 1	1/93 (1.08%)	1
Syncope † 1	1/93 (1.08%)	1
Psychiatric disorders
Agitation † 1	1/93 (1.08%)	1
Anxiety † 1	1/93 (1.08%)	1
Renal and urinary disorders
Acute kidney injury † 1	2/93 (2.15%)	2
Hematuria † 1	2/93 (2.15%)	2
Urinary retention † 1	1/93 (1.08%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	1/93 (1.08%)	2
Bronchopulmonary hemorrhage † 1	1/93 (1.08%)	1
Cough † 1	1/93 (1.08%)	1
Dyspnea † 1	7/93 (7.53%)	7
Hypoxia † 1	1/93 (1.08%)	1
Pleural effusion † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	1/93 (1.08%)	1
Vascular disorders
Thromboembolic event † 1	1/93 (1.08%)	1
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment; [1] Death due to disease progression.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)
	Affected / at Risk (%)	# Events
Total	91/93 (97.85%)
Blood and lymphatic system disorders
Anemia † 1	62/93 (66.67%)	196
Blood and lymphatic system disorders - Other, Adenopathy: supraclavicular node † 1	1/93 (1.08%)	1
Febrile neutropenia † 1	1/93 (1.08%)	1
Lymph node pain † 1	1/93 (1.08%)	1
Cardiac disorders
Cardiac troponin I increased † 1	1/93 (1.08%)	1
Electrocardiogram QT corrected interval prolonged † 1	2/93 (2.15%)	3
Pericardial effusion † 1	1/93 (1.08%)	1
Sinus bradycardia † 1	1/93 (1.08%)	3
Sinus tachycardia † 1	11/93 (11.83%)	34
Ear and labyrinth disorders
Tinnitus † 1	2/93 (2.15%)	2
Vertigo † 1	1/93 (1.08%)	1
Eye disorders
Blurred vision † 1	2/93 (2.15%)	2
Cataract † 1	1/93 (1.08%)	1
Dry eye † 1	2/93 (2.15%)	4
Eye disorders - Other, Non-visibility spots, eye stain † 1	1/93 (1.08%)	1
Eye disorders - Other, Visual changes † 1	1/93 (1.08%)	1
Scleral disorder † 1	1/93 (1.08%)	1
Watering eyes † 1	3/93 (3.23%)	4
Gastrointestinal disorders
Abdominal distension † 1	3/93 (3.23%)	6
Abdominal pain † 1	20/93 (21.51%)	34
Ascites † 1	1/93 (1.08%)	4
Bloating † 1	5/93 (5.38%)	5
Constipation † 1	35/93 (37.63%)	47
Diarrhea † 1	36/93 (38.71%)	81
Dry mouth † 1	8/93 (8.60%)	10
Dyspepsia † 1	1/93 (1.08%)	1
Esophageal pain † 1	1/93 (1.08%)	1
Flatulence † 1	2/93 (2.15%)	2
Gastritis † 1	2/93 (2.15%)	3
Gastroesophageal reflux disease † 1	3/93 (3.23%)	3
Gastrointestinal disorders - Other, "pin point" ulcer on tongue † 1	1/93 (1.08%)	1
Gastrointestinal pain † 1	1/93 (1.08%)	3
Hemorrhoidal hemorrhage † 1	1/93 (1.08%)	1
Hemorrhoids † 1	1/93 (1.08%)	1
Lower gastrointestinal hemorrhage † 1	1/93 (1.08%)	1
Mucositis oral † 1	9/93 (9.68%)	13
Nausea † 1	57/93 (61.29%)	107
Oral hemorrhage † 1	1/93 (1.08%)	1
Vomiting † 1	27/93 (29.03%)	38
Gastrointestinal disorders - Other, Blood in stool † 1	1/93 (1.08%)	1
General disorders
Chills † 1	13/93 (13.98%)	18
Edema face † 1	1/93 (1.08%)	1
Edema limbs † 1	23/93 (24.73%)	25
Fatigue † 1	62/93 (66.67%)	188
Fever † 1	23/93 (24.73%)	53
Flu like symptoms † 1	6/93 (6.45%)	7
Gait disturbance † 1	4/93 (4.30%)	4
Infusion related reaction † 1	1/93 (1.08%)	1
Infusion site extravasation † 1	2/93 (2.15%)	2
Injection site reaction † 1	5/93 (5.38%)	5
Malaise † 1	2/93 (2.15%)	2
Pain † 1	15/93 (16.13%)	25
Hepatobiliary disorders
Hepatobiliary disorders - Other, Cirrhosis † 1	1/93 (1.08%)	1
Immune system disorders
Allergic reaction † 1	1/93 (1.08%)	1
Infections and infestations
Abdominal infection † 1	1/93 (1.08%)	1
Catheter related infection † 1	1/93 (1.08%)	1
Conjunctivitis infective † 1	1/93 (1.08%)	1
Enterocolitis infectious † 1	1/93 (1.08%)	1
Gum infection † 1	1/93 (1.08%)	1
Infections and infestations - Other, C. difficile infection † 1	1/93 (1.08%)	1
Lip infection † 1	1/93 (1.08%)	1
Mucosal infection † 1	2/93 (2.15%)	3
Nail infection † 1	1/93 (1.08%)	1
Paronychia † 1	1/93 (1.08%)	1
Penile infection † 1	1/93 (1.08%)	2
Sinusitis † 1	1/93 (1.08%)	1
Skin infection † 1	2/93 (2.15%)	3
Urinary tract infection † 1	7/93 (7.53%)	10
Vaginal infection † 1	1/93 (1.08%)	2
Wound infection † 1	1/93 (1.08%)	1
Infections and infestations - Other, Herpes † 1	1/93 (1.08%)	1
Infections and infestations - Other, Cryptosporidium † 1	1/93 (1.08%)	1
Infections and infestations - Other, C. difficile colitis † 1	1/93 (1.08%)	1
Infections and infestations - Other, catheter related † 1	1/93 (1.08%)	1
Infections and infestations - Other, Infection with unknown ANC: Blood † 1	1/93 (1.08%)	1
Infections and infestations - Other, Sinusitis † 1	1/93 (1.08%)	1
Injury, poisoning and procedural complications
Bruising † 1	2/93 (2.15%)	3
Fall † 1	4/93 (4.30%)	8
Investigations
Activated partial thromboplastin time prolonged † 1	12/93 (12.90%)	13
Alanine aminotransferase increased † 1	34/93 (36.56%)	83
Alkaline phosphatase increased † 1	26/93 (27.96%)	49
Aspartate aminotransferase increased † 1	36/93 (38.71%)	78
Blood bilirubin increased † 1	8/93 (8.60%)	12
CPK increased † 1	4/93 (4.30%)	10
Creatinine increased † 1	14/93 (15.05%)	29
Hemoglobin increased † 1	2/93 (2.15%)	4
INR increased † 1	4/93 (4.30%)	6
Investigations - Other, Bicarbonate, serum-low † 1	4/93 (4.30%)	5
Lymphocyte count decreased † 1	60/93 (64.52%)	265
Neutrophil count decreased † 1	28/93 (30.11%)	76
Platelet count decreased † 1	37/93 (39.78%)	91
Weight gain † 1	1/93 (1.08%)	2
Weight loss † 1	26/93 (27.96%)	41
White blood cell decreased † 1	49/93 (52.69%)	181
Metabolism and nutrition disorders
Anorexia † 1	37/93 (39.78%)	65
Dehydration † 1	12/93 (12.90%)	17
Hypercalcemia † 1	17/93 (18.28%)	31
Hyperglycemia † 1	10/93 (10.75%)	27
Hyperkalemia † 1	8/93 (8.60%)	20
Hypermagnesemia † 1	9/93 (9.68%)	12
Hypernatremia † 1	4/93 (4.30%)	5
Hyperuricemia † 1	2/93 (2.15%)	3
Hypoalbuminemia † 1	61/93 (65.59%)	174
Hypocalcemia † 1	20/93 (21.51%)	45
Hypoglycemia † 1	8/93 (8.60%)	8
Hypokalemia † 1	23/93 (24.73%)	47
Hypomagnesemia † 1	24/93 (25.81%)	58
Hyponatremia † 1	49/93 (52.69%)	115
Hypophosphatemia † 1	26/93 (27.96%)	49
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/93 (3.23%)	3
Back pain † 1	13/93 (13.98%)	20
Bone pain † 1	4/93 (4.30%)	4
Buttock pain † 1	1/93 (1.08%)	1
Chest wall pain † 1	2/93 (2.15%)	6
Flank pain † 1	3/93 (3.23%)	4
Generalized muscle weakness † 1	6/93 (6.45%)	6
Muscle weakness lower limb † 1	2/93 (2.15%)	2
Muscle weakness upper limb † 1	2/93 (2.15%)	2
Musculoskeletal and connective tissue disorder - Other, locking of fingers-middle and ring † 1	1/93 (1.08%)	1
Myalgia † 1	6/93 (6.45%)	7
Neck pain † 1	2/93 (2.15%)	2
Non-cardiac chest pain † 1	3/93 (3.23%)	4
Pain in extremity † 1	12/93 (12.90%)	18
Trismus † 1	1/93 (1.08%)	1
Musculoskeletal and connective tissue disorder - Other, Swelling - right arm † 1	1/93 (1.08%)	1
Musculoskeletal and connective tissue disorder - Other, chest tightness † 1	1/93 (1.08%)	1
Musculoskeletal and connective tissue disorder - Other, hip pain † 1	1/93 (1.08%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	3/93 (3.23%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1 [1]	1/93 (1.08%)	1
Nervous system disorders
Cognitive disturbance † 1	1/93 (1.08%)	1
Dizziness † 1	12/93 (12.90%)	13
Dysarthria † 1	1/93 (1.08%)	1
Dysesthesia † 1	1/93 (1.08%)	1
Dysgeusia † 1	9/93 (9.68%)	10
Dysphagia † 1	2/93 (2.15%)	2
Headache † 1	13/93 (13.98%)	16
Lethargy † 1	1/93 (1.08%)	1
Memory impairment † 1	2/93 (2.15%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1 [2]	1/93 (1.08%)	1
Nervous system disorders - Other, saddle anesthesia † 1	1/93 (1.08%)	1
Neuralgia † 1	1/93 (1.08%)	1
Paresthesia † 1	1/93 (1.08%)	1
Peripheral motor neuropathy † 1	1/93 (1.08%)	1
Peripheral sensory neuropathy † 1	8/93 (8.60%)	14
Somnolence † 1	3/93 (3.23%)	3
Stroke † 1	1/93 (1.08%)	1
Syncope † 1	1/93 (1.08%)	1
Tremor † 1	2/93 (2.15%)	2
Nervous system disorders - Other, disk replacement † 1	1/93 (1.08%)	1
Psychiatric disorders
Agitation † 1	1/93 (1.08%)	1
Anxiety † 1	6/93 (6.45%)	7
Confusion † 1	3/93 (3.23%)	6
Delirium † 1	1/93 (1.08%)	1
Depression † 1	2/93 (2.15%)	4
Insomnia † 1	8/93 (8.60%)	8
Restlessness † 1	1/93 (1.08%)	1
Renal and urinary disorders
Hematuria † 1	3/93 (3.23%)	4
Proteinuria † 1	1/93 (1.08%)	1
Renal and urinary disorders - Other, renal insufficiency † 1	1/93 (1.08%)	1
Renal calculi † 1	1/93 (1.08%)	1
Urinary frequency † 1	3/93 (3.23%)	4
Urinary retention † 1	2/93 (2.15%)	2
Urinary tract pain † 1	2/93 (2.15%)	2
Renal and urinary disorders - Other, urinary output decreased † 1	1/93 (1.08%)	1
Reproductive system and breast disorders
Genital edema † 1	1/93 (1.08%)	1
Pelvic pain † 1	1/93 (1.08%)	1
Reproductive system and breast disorders - Other, Orchitis † 1	1/93 (1.08%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis † 1	2/93 (2.15%)	3
Aspiration † 1	1/93 (1.08%)	1
Cough † 1	19/93 (20.43%)	30
Dyspnea † 1	24/93 (25.81%)	37
Epistaxis † 1	5/93 (5.38%)	5
Hiccups † 1	1/93 (1.08%)	1
Hoarseness † 1	1/93 (1.08%)	1
Hypoxia † 1	2/93 (2.15%)	3
Pharyngolaryngeal pain † 1	1/93 (1.08%)	1
Pleural effusion † 1	5/93 (5.38%)	6
Pleuritic pain † 1	3/93 (3.23%)	4
Pneumonitis † 1	3/93 (3.23%)	3
Pneumothorax † 1	1/93 (1.08%)	1
Productive cough † 1	5/93 (5.38%)	5
Respiratory, thoracic and mediastinal disorders - Other, Difficulty breathing † 1	1/93 (1.08%)	1
Sore throat † 1	1/93 (1.08%)	1
Upper respiratory infection † 1	3/93 (3.23%)	3
Voice alteration † 1	2/93 (2.15%)	2
Wheezing † 1	2/93 (2.15%)	2
Respiratory, thoracic and mediastinal disorders - Other, nasal drainage † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	2/93 (2.15%)	2
Body odor † 1	1/93 (1.08%)	1
Dry skin † 1	8/93 (8.60%)	11
Erythema multiforme † 1	1/93 (1.08%)	1
Hyperhidrosis † 1	3/93 (3.23%)	3
Nail discoloration † 1	1/93 (1.08%)	1
Palmar-plantar erythrodysesthesia syndrome † 1	4/93 (4.30%)	5
Pruritus † 1	11/93 (11.83%)	11
Rash acneiform † 1	2/93 (2.15%)	2
Rash maculo-papular † 1	7/93 (7.53%)	12
Skin and subcutaneous tissue disorders - Other, Blisters † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, Folliculitis † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, specify † 1 [3]	1/93 (1.08%)	1
Skin hyperpigmentation † 1	2/93 (2.15%)	2
Skin hypopigmentation † 1	1/93 (1.08%)	1
Skin ulceration † 1	2/93 (2.15%)	2
Urticaria † 1	1/93 (1.08%)	2
Skin and subcutaneous tissue disorders - Other, facial erythema † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, scleroderma @ hands and feet † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, nail changes † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, discoloration of leg † 1	1/93 (1.08%)	1
Skin and subcutaneous tissue disorders - Other, rash † 1	1/93 (1.08%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, hip surgery † 1	1/93 (1.08%)	1
Vascular disorders
Hot flashes † 1	1/93 (1.08%)	1
Hypertension † 1	29/93 (31.18%)	175
Hypotension † 1	13/93 (13.98%)	21
Lymphedema † 1	2/93 (2.15%)	2
Superficial thrombophlebitis † 1	1/93 (1.08%)	1
Thromboembolic event † 1	3/93 (3.23%)	4
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment; [1] Complex multiseptated cysts - left testicle; [2] Drainage/bleeding @ chest mass.; [3] Skin and subcutaneous tissue disorder

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. James Doroshow
• Organization: National Cancer Institute
• Phone: 240-781-3320
• EMail: jim_doroshow@nih.gov

Publications:

Lapeyre JN, Becker FF. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun. 1979 Apr 13;87(3):698-705.

Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003 Nov 20;349(21):2042-54. Review.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

• Responsible Party: James Doroshow, M.D., National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00978250
• Other Study ID Numbers: 090214; 09-C-0214
• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Results First Submitted: December 12, 2019
• Results First Posted: December 27, 2019
• Last Update Posted: December 27, 2019