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

January 13, 2020 updated by: Astex Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR) at 16 Weeks for Patients Treated With Guadecitabine After Failure of Sorafenib
Time Frame: 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).
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of Guadecitabine
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
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
Alpha Fetoprotein Response as a Result of Guadecitabine Administration
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
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
Duration of Response
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.
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.
Progression-free Survival
Time Frame: 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.
Through completion of response assessments (i.e., until disease progression or treatment discontinuation), an average of 112 days.
Overall Survival
Time Frame: Through completion of study survival follow-up, an average of 270 days.
Overall survival measured in days.
Through completion of study survival follow-up, an average of 270 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

December 17, 2012

First Submitted That Met QC Criteria

December 17, 2012

First Posted (Estimate)

December 19, 2012

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 13, 2020

Last Verified

January 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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