Back to resultsSGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC)
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SGI-110
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Histological or cytological confirmed hepatocellular carcinoma with advanced stage disease
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Acceptable organ function
- Signed an approved informed consent
Exclusion Criteria:
- Known hypersensitivity to SGI-110
- Adequate washout of prior radiation, chemotherapy or other locoregional therapy
- Abnormal left ventricular ejection fraction
- Uncontrolled ischemic heart disease or a history of congestive cardiac failure
- Known brain metastases
- Clinically evident ascites
- Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points
- 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
- Known history of human immunodeficiency virus (HIV)
Sites / Locations
- City of Hope National Medical Center
- USC Norris Comprehensive Cancer Center
- UC Davis Comprehensive Cancer Center
- H. Lee Moffitt Cancer Center and Research Institute
- Northwestern University: Robert H. Lurie Comprehensive Cancer Center
- University of Louisville James Graham Brown Cancer Center
- Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center
- The Ohio State University Comprehensive Cancer Center
- Fox Chase Cancer Center
- Medical University of South Carolina, Hollings Cancer Center
- The Jones Clinic, PC
- Mary Crowley Medical Research Center
- University of Texas Southwestern Medical Center
- Swedish Cancer Institute
- UW Carbone Cancer Center
- University of British Columbia and Vancouver General Hospital
- The Ottawa Hospital Cancer Center
- Sunnybrook HealthScience Centre
- CHUM Hopital St-Luc
- Centre Hospitalier Universitaire de Sherbrooke
- University of Liverpool Clatterbridge Cancer Center
- Cambridge University Hospitals NHS Foundation Trust
- Imperial College Healthcare NHS Foundation Trust
- University College London
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SGI-110
Arm Description
SGI-110 administered subcutaneously (SC) daily on Days 1 - 5 every 28 days
Outcomes
Primary Outcome Measures
Disease Control Rate (DCR) at 16 Weeks for Patients Treated With Guadecitabine After Failure of Sorafenib
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
Safety and Tolerability of Guadecitabine
Number of patients with serious adverse events and adverse events
Alpha Fetoprotein Response as a Result of Guadecitabine Administration
Percentage of patients with best post baseline alpha fetoprotein reduction of 50% or more
Duration of Response
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.
Progression-free Survival
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.
Overall Survival
Overall survival measured in days.
Full Information
NCT ID
NCT01752933
First Posted
December 17, 2012
Last Updated
January 13, 2020
Sponsor
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01752933
Brief Title
SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC)
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 Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SGI-110
Arm Type
Experimental
Arm Description
SGI-110 administered subcutaneously (SC) daily on Days 1 - 5 every 28 days
Intervention Type
Drug
Intervention Name(s)
SGI-110
Intervention Description
SGI-110 will be administered by subcutaneously (SC) on Days 1 - 5 every 28 days until disease progression or unacceptable toxicity
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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.
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.
Title
Overall Survival
Description
Overall survival measured in days.
Time Frame
Through completion of study survival follow-up, an average of 270 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years of age or older
Histological or cytological confirmed hepatocellular carcinoma with advanced stage disease
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Acceptable organ function
Signed an approved informed consent
Exclusion Criteria:
Known hypersensitivity to SGI-110
Adequate washout of prior radiation, chemotherapy or other locoregional therapy
Abnormal left ventricular ejection fraction
Uncontrolled ischemic heart disease or a history of congestive cardiac failure
Known brain metastases
Clinically evident ascites
Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points
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
Known history of human immunodeficiency virus (HIV)
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern University: Robert H. Lurie Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Louisville James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40201
Country
United States
Facility Name
Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Medical University of South Carolina, Hollings Cancer Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
The Jones Clinic, PC
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
UW Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
University of British Columbia and Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
The Ottawa Hospital Cancer Center
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Sunnybrook HealthScience Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
CHUM Hopital St-Luc
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1N 5N4
Country
Canada
Facility Name
University of Liverpool Clatterbridge Cancer Center
City
Liverpool
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 4AD
Country
United Kingdom
Facility Name
Imperial College Healthcare NHS Foundation Trust
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
Facility Name
University College London
City
London
ZIP/Postal Code
WC1E 6BT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC)
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