SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC)

• Sponsor: Astex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01752933
• Collaborator: (none)
• Enrollment: 52
• Locations: 24
• Arm: 1
• Duration (Months): 33
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A Phase 2 open-label, single-arm, non-randomized study in the treatment of advanced hepatocellular carcinoma (HCC) patients who failed prior treatment with sorafenib using a Simon's 2-stage design. A set minimum number of patients must demonstrate disease control at 16 weeks to proceed to Stage 2. At Stage 2, a set number of patients must have disease control at 16 weeks to declare that SGI-110 is of interest in the treatment of advanced HCC after failure of prior sorafenib.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: SGI-110	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC) Subjects Who Failed Prior Treatment With Sorafenib
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SGI-110 SGI-110 administered subcutaneously (SC) daily on Days 1 - 5 every 28 days	Drug: SGI-110; SGI-110 will be administered by subcutaneously (SC) on Days 1 - 5 every 28 days until disease progression or unacceptable toxicity

Outcome Measures

Primary Outcome Measures

1. Disease Control Rate (DCR) at 16 Weeks for Patients Treated With Guadecitabine After Failure of Sorafenib [16 weeks]

   Percentage of patients achieving a best overall response of complete response (CR) or partial response (PR) plus subjects with stable disease at 16 weeks after the start of treatment. Response was assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for target and non-target lesions using computed tomography (CT) or magnetic resonance imaging (MRI) as follows: Complete Response (CR), disappearance of all target lesions, disappearance of all non-target lesions, and normalization of tumor marker level; Partial Response (PR), at least a 30% decrease in the sum of diameters of target lesions from baseline; Progressive Disease (PD), at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions, and unequivocal progression of non-target lesions; Stable Disease, neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD (Eisenhauer et al. 2009, Eur. J. Cancer 45:228-247).

Secondary Outcome Measures

1. Safety and Tolerability of Guadecitabine [Varied by patient (median number of treatment cycles was 2.0 (range 2-8) in 60 mg/m^2 group, and 4.0 (range 1-13) in 45 mg/m^2 group]

   Number of patients with serious adverse events and adverse events

2. Alpha Fetoprotein Response as a Result of Guadecitabine Administration [Varied by patient (median number of treatment cycles was 2.0 (range 2-8) in 60 mg/m^2 group, and 4.0 (range 1-13) in 45 mg/m^2 group]

   Percentage of patients with best post baseline alpha fetoprotein reduction of 50% or more

3. Duration of Response [From time of first response until disease progression or date of death due to any cause, whichever occurred earlier; an average of 192 days.]

   Duration of response as measured in days. Included subjects with a complete response or partial response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

4. Progression-free Survival [Through completion of response assessments (i.e., until disease progression or treatment discontinuation), an average of 112 days.]

   Progression-free survival measured in days. Progression-free survival was defined as the time interval from the date of the first dose of study treatment to the earlier of 1) documented radiologic progression per RECIST v1.1 or clinical progression, or 2) death due to any cause.

5. Overall Survival [Through completion of study survival follow-up, an average of 270 days.]

   Overall survival measured in days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years of age or older

2. Histological or cytological confirmed hepatocellular carcinoma with advanced stage disease

3. Received prior sorafenib treatment, and showed evidence of disease progression, which is defined as Investigator verified radiologic progression, or intolerance of prior systemic therapy, which is defined as having had clinically significant adverse events that persisted despite one or more dose reductions or interruptions

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. Acceptable organ function

6. Signed an approved informed consent

Exclusion Criteria:

1. Known hypersensitivity to SGI-110

2. Adequate washout of prior radiation, chemotherapy or other locoregional therapy

3. Abnormal left ventricular ejection fraction

4. Uncontrolled ischemic heart disease or a history of congestive cardiac failure

5. Known brain metastases

6. Clinically evident ascites

7. Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points

8. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, non-metastatic prostate cancer with normal prostate-specific antigen (PSA) or other cancer from which the subject has been disease free for at least three years

9. Known history of human immunodeficiency virus (HIV)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
4	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
5	Northwestern University: Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
6	University of Louisville James Graham Brown Cancer Center	Louisville	Kentucky	United States	40201
7	Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
8	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
9	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
10	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina	United States	29425
11	The Jones Clinic, PC	Germantown	Tennessee	United States	38138
12	Mary Crowley Medical Research Center	Dallas	Texas	United States	75230
13	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
14	Swedish Cancer Institute	Seattle	Washington	United States	98122
15	UW Carbone Cancer Center	Madison	Wisconsin	United States	53792
16	University of British Columbia and Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
17	The Ottawa Hospital Cancer Center	Ottawa	Ontario	Canada	K1H 8L6
18	Sunnybrook HealthScience Centre	Toronto	Ontario	Canada	M4N 3M5
19	CHUM Hopital St-Luc	Montreal	Quebec	Canada	H2X 3J4
20	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1N 5N4
21	University of Liverpool Clatterbridge Cancer Center	Liverpool		United Kingdom
22	Cambridge University Hospitals NHS Foundation Trust	London		United Kingdom	EC1V 4AD
23	Imperial College Healthcare NHS Foundation Trust	London		United Kingdom	W12 0NN
24	University College London	London		United Kingdom	WC1E 6BT

Sponsors and Collaborators

• Astex Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Astex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01752933
• Other Study ID Numbers: SGI-110-03
• First Posted: Dec 19, 2012
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Guadecitabine

Study Results

Participant Flow

Recruitment Details	A total of 68 patients were screened for enrollment in the study. Of these, 16 were screen failures. Reasons for screen failure included not meeting all eligibility criteria (14 patients) and withdrawal of consent (2 patients).
Pre-assignment Detail	Of the 52 patients enrolled in the study, 2 did not receive any treatment. Reasons for not receiving treatment included death for one patient and no longer meeting eligibility criteria for the second patient.

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 subcutaneously (SC) on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Period Title: Treatment
STARTED	4	46
COMPLETED	0	0
NOT COMPLETED	4	46
Period Title: Treatment
STARTED	4	46
COMPLETED	0	0
NOT COMPLETED	4	46

Baseline Characteristics

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2	Total
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Total of all reporting groups
Overall Participants	4	46	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	33 71.7%	37 74%
>=65 years	0 0%	13 28.3%	13 26%
Sex: Female, Male (Count of Participants)
Female	0 0%	7 15.2%	7 14%
Male	4 100%	39 84.8%	43 86%
Region of Enrollment (participants) [Number]
Canada	0 0%	7 15.2%	7 14%
United States	4 100%	39 84.8%	43 86%

Outcome Measures

1. Primary Outcome

Title	Disease Control Rate (DCR) at 16 Weeks for Patients Treated With Guadecitabine After Failure of Sorafenib
Description	Percentage of patients achieving a best overall response of complete response (CR) or partial response (PR) plus subjects with stable disease at 16 weeks after the start of treatment. Response was assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for target and non-target lesions using computed tomography (CT) or magnetic resonance imaging (MRI) as follows: Complete Response (CR), disappearance of all target lesions, disappearance of all non-target lesions, and normalization of tumor marker level; Partial Response (PR), at least a 30% decrease in the sum of diameters of target lesions from baseline; Progressive Disease (PD), at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions, and unequivocal progression of non-target lesions; Stable Disease, neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD (Eisenhauer et al. 2009, Eur. J. Cancer 45:228-247).
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Patients who met major inclusion/exclusion criteria and followed the study protocol without a significant deviation (1 patient excluded because did not have confirmed HCC; 4 patients excluded because did not have a Week 16 assessment).

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 on Days 1 - 5 of each 28-day cycle
Measure Participants	4	41
Number (95% Confidence Interval) [percentage of patients]	25.0	24.4

2. Secondary Outcome

Title	Safety and Tolerability of Guadecitabine
Description	Number of patients with serious adverse events and adverse events
Time Frame	Varied by patient (median number of treatment cycles was 2.0 (range 2-8) in 60 mg/m^2 group, and 4.0 (range 1-13) in 45 mg/m^2 group

Outcome Measure Data

Analysis Population Description

Includes all patients who received any guadecitabine

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Measure Participants	4	46
Serious Adverse Event	1 25%	21 45.7%
Adverse Event	4 100%	46 100%

3. Secondary Outcome

Title	Alpha Fetoprotein Response as a Result of Guadecitabine Administration
Description	Percentage of patients with best post baseline alpha fetoprotein reduction of 50% or more
Time Frame	Varied by patient (median number of treatment cycles was 2.0 (range 2-8) in 60 mg/m^2 group, and 4.0 (range 1-13) in 45 mg/m^2 group

Outcome Measure Data

Analysis Population Description

Includes all patients who received any guadecitabine

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Measure Participants	4	46
Count of Participants [Participants]	0 0%	2 4.3%

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response as measured in days. Included subjects with a complete response or partial response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame	From time of first response until disease progression or date of death due to any cause, whichever occurred earlier; an average of 192 days.

Outcome Measure Data

Analysis Population Description

Assessed for patients who had a clinical response

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Measure Participants	1	10
Median (95% Confidence Interval) [days]	262	144

5. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival measured in days. Progression-free survival was defined as the time interval from the date of the first dose of study treatment to the earlier of 1) documented radiologic progression per RECIST v1.1 or clinical progression, or 2) death due to any cause.
Time Frame	Through completion of response assessments (i.e., until disease progression or treatment discontinuation), an average of 112 days.

Outcome Measure Data

Analysis Population Description

Includes all patients who received any guadecitabine

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Measure Participants	4	46
Median (95% Confidence Interval) [days]	55	82.5

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival measured in days.
Time Frame	Through completion of study survival follow-up, an average of 270 days.

Outcome Measure Data

Analysis Population Description

Includes all patients who received any guadecitabine

Arm/Group Title	Guadecitabine 60 mg/m^2	Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle	Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
Measure Participants	4	46
Median (95% Confidence Interval) [days]	294	245

Adverse Events

Time Frame	Treatment-emergent adverse events included events that first occurred or worsened after the first dose of study drug until 30 days after the last dose of study drug or the start of alternative anticancer treatment for HCC, whichever occurred first. Events that occurred more than 30 days after the last dose of study treatment or start of alternative cancer treatment were also considered treatment emergent if they were both serious and related to treatment.
Arm/Group Title	Guadecitabine 60 mg/m^2		Guadecitabine 45 mg/m^2
Arm/Group Description	Guadecitabine (SGI-110) 60 mg/m^2 SC on Days 1 - 5 of each 28-day cycle		Guadecitabine (SGI-110) 45 mg/m^2 SC on Days 1 - 5 of each 28-day cycle
All Cause Mortality
	Guadecitabine 60 mg/m^2		Guadecitabine 45 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		34/46 (73.9%)
Serious Adverse Events
	Guadecitabine 60 mg/m^2		Guadecitabine 45 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		21/46 (45.7%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		1/46 (2.2%)
Febrile neutropenia	1/4 (25%)		5/46 (10.9%)
Cardiac disorders
Atrial fibrillation	0/4 (0%)		1/46 (2.2%)
Endocrine disorders
Adrenal haemorrhage	0/4 (0%)		1/46 (2.2%)
Gastrointestinal disorders
Abdominal pain	0/4 (0%)		2/46 (4.3%)
Ascites	0/4 (0%)		1/46 (2.2%)
Diarrhoea	0/4 (0%)		1/46 (2.2%)
Gastrointestinal haemorrhage	0/4 (0%)		1/46 (2.2%)
Nausea	0/4 (0%)		1/46 (2.2%)
Oesophagitis	0/4 (0%)		1/46 (2.2%)
Upper gastrointestinal haemorrhage	0/4 (0%)		1/46 (2.2%)
Vomiting	0/4 (0%)		1/46 (2.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/4 (0%)		1/46 (2.2%)
Portal vein thrombosis	0/4 (0%)		1/46 (2.2%)
Infections and infestations
Pneumonia	0/4 (0%)		1/46 (2.2%)
Staphylococcal sepsis	0/4 (0%)		1/46 (2.2%)
Injury, poisoning and procedural complications
Road traffic accident	0/4 (0%)		2/46 (4.3%)
Investigations
Blood creatinine increased	0/4 (0%)		1/46 (2.2%)
Metabolism and nutrition disorders
Hyponatremia	0/4 (0%)		1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/4 (0%)		2/46 (4.3%)
Nervous system disorders
Hepatic encephalopathy	0/4 (0%)		1/46 (2.2%)
Renal and urinary disorders
Nephrolithiasis	0/4 (0%)		1/46 (2.2%)
Renal failure acute	0/4 (0%)		1/46 (2.2%)
Reproductive system and breast disorders
Scrotal pain	0/4 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/4 (0%)		1/46 (2.2%)
Respiratory failure	0/4 (0%)		1/46 (2.2%)
Vascular disorders
Hypotension	0/4 (0%)		1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Guadecitabine 60 mg/m^2		Guadecitabine 45 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		46/46 (100%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)		11/46 (23.9%)
Leukopenia	1/4 (25%)		21/46 (45.7%)
Lymphopenia	0/4 (0%)		10/46 (21.7%)
Neutropenia	4/4 (100%)		39/46 (84.8%)
Thrombocytopenia	4/4 (100%)		20/46 (43.5%)
Cardiac disorders
Atrial fibrillation	1/4 (25%)		0/46 (0%)
Ear and labyrinth disorders
Vertigo	1/4 (25%)		0/46 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/4 (25%)		2/46 (4.3%)
Abdominal distension	0/4 (0%)		7/46 (15.2%)
Abdominal pain	1/4 (25%)		8/46 (17.4%)
Abdominal pain upper	1/4 (25%)		4/46 (8.7%)
Ascites	0/4 (0%)		3/46 (6.5%)
Constipation	0/4 (0%)		11/46 (23.9%)
Diarrhoea	2/4 (50%)		11/46 (23.9%)
Nausea	2/4 (50%)		11/46 (23.9%)
Stomatitis	1/4 (25%)		3/46 (6.5%)
Vomiting	1/4 (25%)		9/46 (19.6%)
Abdominal tenderness	1/4 (25%)		1/46 (2.2%)
Gingival swelling	1/4 (25%)		0/46 (0%)
Glossodynia	1/4 (25%)		0/46 (0%)
General disorders
Chills	0/4 (0%)		5/46 (10.9%)
Early satiety	0/4 (0%)		3/46 (6.5%)
Fatigue	3/4 (75%)		24/46 (52.2%)
Injection site erythema	2/4 (50%)		3/46 (6.5%)
Injection site haematoma	1/4 (25%)		3/46 (6.5%)
Injection site pain	2/4 (50%)		21/46 (45.7%)
Injection site reaction	0/4 (0%)		6/46 (13%)
Mucosal inflammation	1/4 (25%)		2/46 (4.3%)
Non-cardiac chest pain	1/4 (25%)		2/46 (4.3%)
Oedema peripheral	1/4 (25%)		9/46 (19.6%)
Pyrexia	1/4 (25%)		9/46 (19.6%)
Asthenia	1/4 (25%)		1/46 (2.2%)
Injection site induration	1/4 (25%)		0/46 (0%)
Injection site pruritus	1/4 (25%)		0/46 (0%)
Pain	1/4 (25%)		1/46 (2.2%)
Hepatobiliary disorders
Hyperbilirubinemia	0/4 (0%)		5/46 (10.9%)
Infections and infestations
Urinary tract infection	0/4 (0%)		4/46 (8.7%)
Injury, poisoning and procedural complications
Fall	0/4 (0%)		3/46 (6.5%)
Investigations
Alanine aminotransferase increased	0/4 (0%)		8/46 (17.4%)
Aspartate aminotransferase increased	1/4 (25%)		14/46 (30.4%)
Blood alkaline phosphatase increased	1/4 (25%)		10/46 (21.7%)
Blood bilirubin increased	0/4 (0%)		4/46 (8.7%)
Hypoalbuminemia	0/4 (0%)		3/46 (6.5%)
Weight decreased	0/4 (0%)		4/46 (8.7%)
Weight increased	0/4 (0%)		3/46 (6.5%)
Metabolism and nutrition disorders
Decreased appetite	1/4 (25%)		9/46 (19.6%)
Hyperglycaemia	0/4 (0%)		7/46 (15.2%)
Hyperkalaemia	0/4 (0%)		3/46 (6.5%)
Hypoalbuminaemia	0/4 (0%)		5/46 (10.9%)
Hypocalcaemia	0/4 (0%)		3/46 (6.5%)
Hypoglycaemia	0/4 (0%)		3/46 (6.5%)
Hypokalaemia	0/4 (0%)		3/46 (6.5%)
Hypomagnesaemia	0/4 (0%)		3/46 (6.5%)
Hyponatraemia	0/4 (0%)		6/46 (13%)
Hypophosphataemia	0/4 (0%)		4/46 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		5/46 (10.9%)
Back pain	1/4 (25%)		10/46 (21.7%)
Bone pain	2/4 (50%)		2/46 (4.3%)
Myalgia	1/4 (25%)		2/46 (4.3%)
Neck pain	0/4 (0%)		3/46 (6.5%)
Pain in extremity	1/4 (25%)		5/46 (10.9%)
Nervous system disorders
Dizziness	1/4 (25%)		6/46 (13%)
Dysgeusia	2/4 (50%)		1/46 (2.2%)
Headache	2/4 (50%)		6/46 (13%)
Neuropathy peripheral	0/4 (0%)		3/46 (6.5%)
Psychiatric disorders
Insomnia	1/4 (25%)		4/46 (8.7%)
Mental status changes	0/4 (0%)		3/46 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/4 (25%)		12/46 (26.1%)
Dyspnoea	1/4 (25%)		6/46 (13%)
Oropharyngeal pain	0/4 (0%)		3/46 (6.5%)
Hypoxia	1/4 (25%)		1/46 (2.2%)
Wheezing	1/4 (25%)		1/46 (2.2%)
Skin and subcutaneous tissue disorders
Pruritus	0/4 (0%)		3/46 (6.5%)
Rash	0/4 (0%)		5/46 (10.9%)
Petechiae	1/4 (25%)		0/46 (0%)
Vascular disorders
Hypertension	0/4 (0%)		8/46 (17.4%)
Hypotension	0/4 (0%)		5/46 (10.9%)

Limitations/Caveats

The original starting dose of 60 mg/m^2 guadecitabine was reduced to 45 mg/m^2 after dose-limiting toxicities occurred in the first 4 patients.

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.