HCC, Hepatocellular Carcinoma, Liver Cancer
Conditions
Keywords
liver cancer, liver tumor, hepatocellular cancer, Jennerex, HCC, Advanced HCC, sorafenib, sorafenib failure, sorafenib intolerant, Nexavar, Nexavar failure, JX594, oncolytic virus, viral therapy, JX, Biotherapeutics, vaccinia, HEP018, traverse, biologic, Pexa-Vec
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALJX-594 recombinant vaccina GM-CSF
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.
OTHERBest Supportive Care
Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.
Sponsors
Jennerex Biotherapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
KEY Inclusion Criteria: * Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis * Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC * ECOG performance status 0, 1 or 2 * Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites * Hematocrit ≥30% or Hemoglobin ≥10 g/dL * Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited \>25% growth in viable tumor size since prior local-regional treatment. KEY
Exclusion criteria
* Received sorafenib within 14 days prior to randomization * Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization * Prior treatment with JX-594 * Platelet count \< 50,000 PLT/ mm3 * Total white blood cell count \< 2,000 cells/mm3 * Prior or planned organ transplant * Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication * Severe or unstable cardiac disease * Viable CNS malignancy associated with clinical symptoms * Pregnant or nursing an infant * History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
Countries
Canada, France, Germany, Hong Kong, South Korea, Taiwan, United States
Contacts
STUDY_DIRECTORJames Burke, MD
Jennerex Biotherapeutics
Outcome results
None listed