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

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 2 Study of SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC) Subjects Who Failed Prior Treatment With Sorafenib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01752933
• Other study ID #: SGI-110-03
• Status: Completed
• Phase: Phase 2
• Start date: December 2012
• Est. completion date: September 2015

Study information

• Verified date: January 2020
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• SGI-110
SGI-110 will be administered by subcutaneously (SC) on Days 1 - 5 every 28 days until disease progression or unacceptable toxicity

Locations

Country	Name	City	State
Canada	CHUM Hopital St-Luc	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Center	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Sunnybrook HealthScience Centre	Toronto	Ontario
Canada	University of British Columbia and Vancouver General Hospital	Vancouver	British Columbia
United Kingdom	University of Liverpool Clatterbridge Cancer Center	Liverpool
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Foundation Trust	London
United Kingdom	University College London	London
United States	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina
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	Mary Crowley Medical Research Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	The Jones Clinic, PC	Germantown	Tennessee
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Louisville James Graham Brown Cancer Center	Louisville	Kentucky
United States	UW Carbone Cancer Center	Madison	Wisconsin
United States	Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	16 weeks
Secondary	Safety and Tolerability of Guadecitabine	Number of patients with serious adverse events and adverse events	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
Secondary	Alpha Fetoprotein Response as a Result of Guadecitabine Administration	Percentage of patients with best post baseline alpha fetoprotein reduction of 50% or more	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
Secondary	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.	From time of first response until disease progression or date of death due to any cause, whichever occurred earlier; an average of 192 days.
Secondary	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.	Through completion of response assessments (i.e., until disease progression or treatment discontinuation), an average of 112 days.
Secondary	Overall Survival	Overall survival measured in days.	Through completion of study survival follow-up, an average of 270 days.