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

• ClinicalTrials.gov Identifier: NCT01752933
• Recruitment Status: Completed
• First Posted: December 19, 2012
• Results First Posted: July 30, 2019
• Last Update Posted: January 18, 2020
• Sponsor: Astex Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Astex Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: December 17, 2012
• First Posted Date: December 19, 2012
• Results First Submitted Date: May 30, 2019
• Results First Posted Date: July 30, 2019
• Last Update Posted Date: January 18, 2020
• Study Start Date: December 2012
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 8, 2019)

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).

Original Primary Outcome Measures (submitted: December 17, 2012)

Assess the disease control rate (DCR) at 16 weeks for patients treated with SGI-110 after failure of sorafenib [ Time Frame: 18 months ]

Percentage of patients achieving a best overall response of complete response or partial response and stable disease at 16 weeks

Current Secondary Outcome Measures (submitted: July 8, 2019)

• 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
• 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
• 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.
• 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.
• Overall Survival [ Time Frame: Through completion of study survival follow-up, an average of 270 days. ]
  Overall survival measured in days.

Original Secondary Outcome Measures (submitted: December 17, 2012)

• Assess safety and tolerability of SGI-110 [ Time Frame: 18 months ]
  Number of patients with serious adverse events and adverse events
• Determine alpha fetoprotein response as a result of SGI-110 administration [ Time Frame: 18 months ]
  Change in alpha fetoprotein levels from pre-treatment levels
• Duration of response, progression-free survival, overall survival [ Time Frame: 18 months ]
  Duration of response as measured in weeks. Progression-free survival and overall survival measured in weeks.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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

Study Arms

Experimental: SGI-110

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

Intervention: Drug: SGI-110

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 8, 2019): 52
• Original Estimated Enrollment (submitted: December 17, 2012): 46
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United Kingdom, United States
• Removed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT01752933
• Other Study ID Numbers: SGI-110-03
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Astex Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Astex Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Astex Pharmaceuticals, Inc.
• Verification Date: January 2020