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

NCT01752933 | Completed Phase 2 Results

• 1 other identifier: SGI-110-03
• Study Type: interventional
• Target: 52
• Locations: 3 countries
• Sites: 24

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• 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

• 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.

• Progression-free Survival

  Through completion of response assessments (i.e., until disease progression or treatment discontinuation), an average of 112 days.

• Overall Survival

  Through completion of study survival follow-up, an average of 270 days.

Study Arms (1)

SGI-110

EXPERIMENTAL

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

Drug: SGI-110

Interventions

SGI-110 DRUG

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

SGI-110

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (24)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Northwestern University: Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40201, United States

Location

Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

The Jones Clinic, PC

Germantown, Tennessee, 38138, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98122, United States

Location

UW Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

University of British Columbia and Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

The Ottawa Hospital Cancer Center

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook HealthScience Centre

Toronto, Ontario, M4N 3M5, Canada

Location

CHUM Hopital St-Luc

Montreal, Quebec, H2X 3J4, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1N 5N4, Canada

Location

University of Liverpool Clatterbridge Cancer Center

Liverpool, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

London, EC1V 4AD, United Kingdom

Location

Imperial College Healthcare NHS Foundation Trust

London, W12 0NN, United Kingdom

Location

University College London

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

The original starting dose of 60 mg/m\^2 guadecitabine was reduced to 45 mg/m\^2 after dose-limiting toxicities occurred in the first 4 patients.

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

clinicaltrialinfo@taihooncology.com

609-250-7336

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: December 19, 2012
• Study Start: December 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: August 27, 2024
• Results First Posted: July 30, 2019

Record last verified: 2024-07

Locations

GB (4); US (15); CA (5)