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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: SGI-110


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 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 | 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 | 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 | 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 | 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 | Overall survival measured in days. | Through completion of study survival follow-up, an average of 270 days. |