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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01752933
Recruitment Status : Completed
First Posted : December 19, 2012
Results First Posted : July 30, 2019
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Intervention Drug: SGI-110
Enrollment 52
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 Details 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
Hide 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 [1] 4 [2] 46 [2]
Completed [3] 0 [4] 0 [4]
Not Completed 4 46
Reason Not Completed
Disease Progression             3             29
Withdrawal by Subject             0             5
Adverse Event             1             4
Physician Decision             0             3
Death             0             2
Hepatocellular carcinoma not confirmed             0             1
Patient noncompliant             0             1
Patient unable to travel to appointments             0             1
[1]
"Reason Not Completed" shown below are reasons for treatment discontinuation
[2]
Includes all patients who received any treatment
[3]
Treatment continued as long as patient was benefitting from treatment with manageable side effects
[4]
Completion not applicable for this survival study
Period Title: Overall Study and Follow-up
Started [1] 4 [2] 46 [2]
Completed 0 [3] 0 [3]
Not Completed 4 46
Reason Not Completed
Death             4             34
Sponsor terminated study/Database lock             0             7
Withdrawal by Subject             0             3
Lost to Follow-up             0             2
[1]
"Reason Not Completed" shown below are reasons for study discontinuation
[2]
Includes all patients who received any treatment
[3]
Completion not applicable for this survival study
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2 Total
Hide 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 Number of Baseline Participants 4 46 50
Hide Baseline Analysis Population Description
The total number of subjects presented for Baseline Analysis (50 subjects) is less than the total presented in Participant Flow (52 subjects) because 2 subjects were withdrawn from the study prior to receiving treatment and thus were not assigned to a treatment group.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 46 participants 50 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
33
  71.7%
37
  74.0%
>=65 years
0
   0.0%
13
  28.3%
13
  26.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 46 participants 50 participants
Female
0
   0.0%
7
  15.2%
7
  14.0%
Male
4
 100.0%
39
  84.8%
43
  86.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 4 participants 46 participants 50 participants
Canada 0 7 7
United States 4 39 43
1.Primary Outcome
Title Disease Control Rate (DCR) at 16 Weeks for Patients Treated With Guadecitabine After Failure of Sorafenib
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 4 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
25.0
(0.6 to 80.6)
24.4
(12.4 to 40.3)
2.Secondary Outcome
Title Safety and Tolerability of Guadecitabine
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all patients who received any guadecitabine
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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
Overall Number of Participants Analyzed 4 46
Measure Type: Count of Participants
Unit of Measure: Participants
Serious Adverse Event
1
  25.0%
21
  45.7%
Adverse Event
4
 100.0%
46
 100.0%
3.Secondary Outcome
Title Alpha Fetoprotein Response as a Result of Guadecitabine Administration
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all patients who received any guadecitabine
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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
Overall Number of Participants Analyzed 4 46
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
   4.3%
4.Secondary Outcome
Title Duration of Response
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Assessed for patients who had a clinical response
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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
Overall Number of Participants Analyzed 1 10
Median (95% Confidence Interval)
Unit of Measure: days
262
144
(109.0 to 240.0)
5.Secondary Outcome
Title Progression-free Survival
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all patients who received any guadecitabine
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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
Overall Number of Participants Analyzed 4 46
Median (95% Confidence Interval)
Unit of Measure: days
55
(50.0 to 262.0)
82.5
(57.0 to 113.0)
6.Secondary Outcome
Title Overall Survival
Hide Description Overall survival measured in days.
Time Frame Through completion of study survival follow-up, an average of 270 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all patients who received any guadecitabine
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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
Overall Number of Participants Analyzed 4 46
Median (95% Confidence Interval)
Unit of Measure: days
294
(103.0 to 683.0)
245
(148.0 to 303.0)
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Hide 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 (%) Affected / at Risk (%)
Total   4/4 (100.00%)   34/46 (73.91%) 
Hide Serious Adverse Events
Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Affected / at Risk (%) Affected / at Risk (%)
Total   1/4 (25.00%)   21/46 (45.65%) 
Blood and lymphatic system disorders     
Anaemia † 1  0/4 (0.00%)  1/46 (2.17%) 
Febrile neutropenia † 1  1/4 (25.00%)  5/46 (10.87%) 
Cardiac disorders     
Atrial fibrillation † 1  0/4 (0.00%)  1/46 (2.17%) 
Endocrine disorders     
Adrenal haemorrhage † 1  0/4 (0.00%)  1/46 (2.17%) 
Gastrointestinal disorders     
Abdominal pain † 1  0/4 (0.00%)  2/46 (4.35%) 
Ascites † 1  0/4 (0.00%)  1/46 (2.17%) 
Diarrhoea † 1  0/4 (0.00%)  1/46 (2.17%) 
Gastrointestinal haemorrhage † 1  0/4 (0.00%)  1/46 (2.17%) 
Nausea † 1  0/4 (0.00%)  1/46 (2.17%) 
Oesophagitis † 1  0/4 (0.00%)  1/46 (2.17%) 
Upper gastrointestinal haemorrhage † 1  0/4 (0.00%)  1/46 (2.17%) 
Vomiting † 1  0/4 (0.00%)  1/46 (2.17%) 
Hepatobiliary disorders     
Hyperbilirubinaemia † 1  0/4 (0.00%)  1/46 (2.17%) 
Portal vein thrombosis † 1  0/4 (0.00%)  1/46 (2.17%) 
Infections and infestations     
Pneumonia † 1  0/4 (0.00%)  1/46 (2.17%) 
Staphylococcal sepsis † 1  0/4 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications     
Road traffic accident † 1  0/4 (0.00%)  2/46 (4.35%) 
Investigations     
Blood creatinine increased † 1  0/4 (0.00%)  1/46 (2.17%) 
Metabolism and nutrition disorders     
Hyponatremia † 1  0/4 (0.00%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity † 1  0/4 (0.00%)  2/46 (4.35%) 
Nervous system disorders     
Hepatic encephalopathy † 1  0/4 (0.00%)  1/46 (2.17%) 
Renal and urinary disorders     
Nephrolithiasis † 1  0/4 (0.00%)  1/46 (2.17%) 
Renal failure acute † 1  0/4 (0.00%)  1/46 (2.17%) 
Reproductive system and breast disorders     
Scrotal pain † 1  0/4 (0.00%)  1/46 (2.17%) 
Respiratory, thoracic and mediastinal disorders     
Hypoxia † 1  0/4 (0.00%)  1/46 (2.17%) 
Respiratory failure † 1  0/4 (0.00%)  1/46 (2.17%) 
Vascular disorders     
Hypotension † 1  0/4 (0.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA 14.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Guadecitabine 60 mg/m^2 Guadecitabine 45 mg/m^2
Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   46/46 (100.00%) 
Blood and lymphatic system disorders     
Anaemia † 1  1/4 (25.00%)  11/46 (23.91%) 
Leukopenia † 1  1/4 (25.00%)  21/46 (45.65%) 
Lymphopenia † 1  0/4 (0.00%)  10/46 (21.74%) 
Neutropenia † 1  4/4 (100.00%)  39/46 (84.78%) 
Thrombocytopenia † 1  4/4 (100.00%)  20/46 (43.48%) 
Cardiac disorders     
Atrial fibrillation † 1  1/4 (25.00%)  0/46 (0.00%) 
Ear and labyrinth disorders     
Vertigo † 1  1/4 (25.00%)  0/46 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort † 1  1/4 (25.00%)  2/46 (4.35%) 
Abdominal distension † 1  0/4 (0.00%)  7/46 (15.22%) 
Abdominal pain † 1  1/4 (25.00%)  8/46 (17.39%) 
Abdominal pain upper † 1  1/4 (25.00%)  4/46 (8.70%) 
Ascites † 1  0/4 (0.00%)  3/46 (6.52%) 
Constipation † 1  0/4 (0.00%)  11/46 (23.91%) 
Diarrhoea † 1  2/4 (50.00%)  11/46 (23.91%) 
Nausea † 1  2/4 (50.00%)  11/46 (23.91%) 
Stomatitis † 1  1/4 (25.00%)  3/46 (6.52%) 
Vomiting † 1  1/4 (25.00%)  9/46 (19.57%) 
Abdominal tenderness † 1  1/4 (25.00%)  1/46 (2.17%) 
Gingival swelling † 1  1/4 (25.00%)  0/46 (0.00%) 
Glossodynia † 1  1/4 (25.00%)  0/46 (0.00%) 
General disorders     
Chills † 1  0/4 (0.00%)  5/46 (10.87%) 
Early satiety † 1  0/4 (0.00%)  3/46 (6.52%) 
Fatigue † 1  3/4 (75.00%)  24/46 (52.17%) 
Injection site erythema † 1  2/4 (50.00%)  3/46 (6.52%) 
Injection site haematoma † 1  1/4 (25.00%)  3/46 (6.52%) 
Injection site pain † 1  2/4 (50.00%)  21/46 (45.65%) 
Injection site reaction † 1  0/4 (0.00%)  6/46 (13.04%) 
Mucosal inflammation † 1  1/4 (25.00%)  2/46 (4.35%) 
Non-cardiac chest pain † 1  1/4 (25.00%)  2/46 (4.35%) 
Oedema peripheral † 1  1/4 (25.00%)  9/46 (19.57%) 
Pyrexia † 1  1/4 (25.00%)  9/46 (19.57%) 
Asthenia † 1  1/4 (25.00%)  1/46 (2.17%) 
Injection site induration † 1  1/4 (25.00%)  0/46 (0.00%) 
Injection site pruritus † 1  1/4 (25.00%)  0/46 (0.00%) 
Pain † 1  1/4 (25.00%)  1/46 (2.17%) 
Hepatobiliary disorders     
Hyperbilirubinemia † 1  0/4 (0.00%)  5/46 (10.87%) 
Infections and infestations     
Urinary tract infection † 1  0/4 (0.00%)  4/46 (8.70%) 
Injury, poisoning and procedural complications     
Fall † 1  0/4 (0.00%)  3/46 (6.52%) 
Investigations     
Alanine aminotransferase increased † 1  0/4 (0.00%)  8/46 (17.39%) 
Aspartate aminotransferase increased † 1  1/4 (25.00%)  14/46 (30.43%) 
Blood alkaline phosphatase increased † 1  1/4 (25.00%)  10/46 (21.74%) 
Blood bilirubin increased † 1  0/4 (0.00%)  4/46 (8.70%) 
Hypoalbuminemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Weight decreased † 1  0/4 (0.00%)  4/46 (8.70%) 
Weight increased † 1  0/4 (0.00%)  3/46 (6.52%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  1/4 (25.00%)  9/46 (19.57%) 
Hyperglycaemia † 1  0/4 (0.00%)  7/46 (15.22%) 
Hyperkalaemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Hypoalbuminaemia † 1  0/4 (0.00%)  5/46 (10.87%) 
Hypocalcaemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Hypoglycaemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Hypokalaemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Hypomagnesaemia † 1  0/4 (0.00%)  3/46 (6.52%) 
Hyponatraemia † 1  0/4 (0.00%)  6/46 (13.04%) 
Hypophosphataemia † 1  0/4 (0.00%)  4/46 (8.70%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/4 (25.00%)  5/46 (10.87%) 
Back pain † 1  1/4 (25.00%)  10/46 (21.74%) 
Bone pain † 1  2/4 (50.00%)  2/46 (4.35%) 
Myalgia † 1  1/4 (25.00%)  2/46 (4.35%) 
Neck pain † 1  0/4 (0.00%)  3/46 (6.52%) 
Pain in extremity † 1  1/4 (25.00%)  5/46 (10.87%) 
Nervous system disorders     
Dizziness † 1  1/4 (25.00%)  6/46 (13.04%) 
Dysgeusia † 1  2/4 (50.00%)  1/46 (2.17%) 
Headache † 1  2/4 (50.00%)  6/46 (13.04%) 
Neuropathy peripheral † 1  0/4 (0.00%)  3/46 (6.52%) 
Psychiatric disorders     
Insomnia † 1  1/4 (25.00%)  4/46 (8.70%) 
Mental status changes † 1  0/4 (0.00%)  3/46 (6.52%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  1/4 (25.00%)  12/46 (26.09%) 
Dyspnoea † 1  1/4 (25.00%)  6/46 (13.04%) 
Oropharyngeal pain † 1  0/4 (0.00%)  3/46 (6.52%) 
Hypoxia † 1  1/4 (25.00%)  1/46 (2.17%) 
Wheezing † 1  1/4 (25.00%)  1/46 (2.17%) 
Skin and subcutaneous tissue disorders     
Pruritus † 1  0/4 (0.00%)  3/46 (6.52%) 
Rash † 1  0/4 (0.00%)  5/46 (10.87%) 
Petechiae † 1  1/4 (25.00%)  0/46 (0.00%) 
Vascular disorders     
Hypertension † 1  0/4 (0.00%)  8/46 (17.39%) 
Hypotension † 1  0/4 (0.00%)  5/46 (10.87%) 
1
Term from vocabulary, MedDRA 14.0
†
Indicates events were collected by systematic assessment
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.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Harold Keer, Senior Vice President Clinical Development
Organization: Astex Pharmaceuticals, Inc.
Phone: 925-719-0741
EMail: Harold.Keer@astx.com
Layout table for additonal information
Responsible Party: Astex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01752933    
Other Study ID Numbers: SGI-110-03
First Submitted: December 17, 2012
First Posted: December 19, 2012
Results First Submitted: May 30, 2019
Results First Posted: July 30, 2019
Last Update Posted: January 18, 2020