This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.
This Phase 2b, open-label, randomized, multi-center study is designed to evaluate the efficacy and safety of JX-594 (Pexa-Vec) in patients with advanced hepatocellular carcinoma (HCC) who have previously failed sorafenib treatment. Eligible patients are randomly assigned in a 2:1 ratio to receive either the experimental therapy (JX-594 plus Best Supportive Care \[BSC\]) or the control therapy (BSC alone). Patients assigned to the experimental arm receive an initial intravenous (IV) infusion of JX-594 on Day 1. This is followed by intratumoral (IT) injections of JX-594 directly into viable liver tumors under imaging guidance on Day 8, Day 22, and Weeks 6, 12, and 18. These patients will also receive BSC, but active anti-cancer treatments are strictly prohibited. In contrast, patients in the control arm receive only Best Supportive Care (e.g., hydration, nutrition, pain management) at the treating physician's discretion without any study drug injections. Experimental or active anti-cancer therapies are not permitted in the control arm. The primary objective of this study is to compare the Overall Survival (OS) between the two treatment arms. Secondary objectives include evaluating Time-to-Tumor Progression (TTP) and objective response rate based on mRECIST criteria for HCC. The study also evaluates Time-to-Symptomatic Progression (TSP), which is defined by changes in the FACT Hepatobiliary Symptom Index (FHSI-8) questionnaire and ECOG performance status. Additionally, the study assesses changes in Quality of Life (QoL) measured by EORTC and FACT-Hep questionnaires. Finally, overall safety and tolerability are closely monitored through the incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to NCI CTCAE v4.03, along with clinical laboratory evaluations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
129
Patients will be randomised 2:1 to Arm A or Arm B and will receive 6 treatments on days 1, 8, 22, week 6, week 12, and week 18 plus best supportive care as needed.
Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.
Survival
Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.
Time frame: From randomization until death from any cause, assessed up to 21 months.
Time to Tumor Progression
Determine time-to-tumor-progression (TTP) for JX-594 + BSC compared with BSC alone based on mRECIST for HCC. Progression is defined as 2 consecutive time points with increases in the sum of the longest diameters (SLD) of viable target tumors of at least 20% for each time point.
Time frame: CT scan every six weeks until progression or death, assessed up to 21 months
Mean Percent Change From Baseline in Quality of Life (FACT-Hep Score)
Change in Quality of Life (QoL) over time based on the physical well-being and additional concerns domains of the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Questionnaire. The FACT-Hep measures health-related quality of life in patients with hepatobiliary cancer. The item scores from these specific subscales are summed to compute a combined score. The combined score ranges from 0 to 100. Higher scores represent a better quality of life and a better outcome.
Time frame: Baseline to Visit 8 (Week 6 ) and Visit 11 (Week 12)
Overall Disease Control Rate (Tumor Response)
The overall disease control rate is defined as the percentage of patients achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) for Hepatocellular Carcinoma (HCC). Per mRECIST for HCC, CR is the disappearance of any intratumoral arterial enhancement in all target lesions; PR is a \>=30% decrease in the sum of the longest diameters (SLD) of viable target lesions; and SD is disease that does not qualify for either PR or progressive disease. Best response over all time points after Baseline was used.
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Moores University of California San Diego Cancer Center
La Jolla, California, United States
Chao Family Comprehensive Cancer Center
Orange, California, United States
California Pacific Medical Center
San Francisco, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Billings Clinic
Billings, Montana, United States
Saint Joseph's Hospital
Paterson, New Jersey, United States
Montefiore Medical Center
The Bronx, New York, United States
Gabrail Cancer Center
Canton, Ohio, United States
University Hospitals Case Medical Center
Cleveland, Ohio, United States
...and 28 more locations
Time frame: CT scan every 6 weeks until progression or death, assessed up to 21 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to 28 days after the last dose of study drug, assessed up to 14 months.
Time-to-symptomatic-progression
Symptomatic progression is defined as a decrease of 4 points or more from Baseline in the FHSI-8 questionnaire (that was confirmed 3 weeks later), or a decrease in ECOG performance status to 4, or death.
Time frame: From randomization until symptomatic progression or death, assessed up to 21 months