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

Phase 2

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: SGI-110

• Registration Number: NCT01752933
• Lead Sponsor: Astex Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2012-12-17
• Study First Submitted QC: 2012-12-17
• Study First Posted: 2012-12-19
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Disposition First Submitted: 2017-01-24
• Disposition First Submitted QC: 2017-01-24
• Disposition First Posted: 2017-01-26
• Results First Submitted: 2019-05-30
• Results First Submitted QC: 2019-07-08
• Results First Posted: 2019-07-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-31
• Last Update Posted: 2024-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SGI-110	SGI-110	SGI-110 administered subcutaneously (SC) daily on Days 1 - 5 every 28 days

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Overall Survival	Through completion of study survival follow-up, an average of 270 days.	Overall survival measured in days.
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
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
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.

Trial Locations

Locations (24)

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Mary Crowley Medical Research Center; 🇺🇸 Dallas, Texas, United States

Centre Hospitalier Universitaire de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

CHUM Hopital St-Luc; 🇨🇦 Montreal, Quebec, Canada

The Jones Clinic, PC; 🇺🇸 Germantown, Tennessee, United States

University College London; 🇬🇧 London, United Kingdom

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

Northwestern University: Robert H. Lurie Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

The Ottawa Hospital Cancer Center; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook HealthScience Centre; 🇨🇦 Toronto, Ontario, Canada

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

University of Liverpool Clatterbridge Cancer Center; 🇬🇧 Liverpool, United Kingdom

Imperial College Healthcare NHS Foundation Trust; 🇬🇧 London, United Kingdom

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

University of Louisville James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

Medical University of South Carolina, Hollings Cancer Center; 🇺🇸 Charleston, South Carolina, United States

UW Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States

University of British Columbia and Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada