This is a randomized, controlled multi-site, multi-national clinical trial conducted in Thailand and Malaysia for Asian adults (males or females), 18 years of age and older presenting with advanced HCC (BCLC stage C) including subjects with macrovascular involvement and/or extrahepatic spread (not eligible for TACE, surgery or locoregional treatment) with Child-Pugh stage A or B liver function. 150 subjects will be randomized 2:1 to AlloStim® immunotherapy vs Physician's Choice of Sorafenib, Lenvatinib or FOLFOX4.
A multi-national, randomized, controlled trial (RCT) with multiple sites selected in Asia (Malaysia and Thailand). Subjects with no prior treatments for BCLC stage C disease and presenting with Child-Pugh class A or B liver reserve to be randomized 2:1 to AlloStim® vs. Physician's Choice (PC). PC to be declared prior to randomization. PC allowed to be either sorafenib, levantinib or FOLFOX4. The world incidence of hepatocellular carcinoma (HCC) is highest in East and South East Asia, with nearly half of the all HCC cases and deaths globally occurring in China. In Asian countries, the main treatment options for early or intermediate HCC (BCLC class A and B) include surgical resection, ablation (e.g., RFA, ETOH, cryoablation), transarterial chemoembolization (TACE), radiation or systemic chemotherapy depending on liver function status. However, in the Asian-Pacific region it is estimated that up to 80% of patients present with unresectable, advanced HCC (BCLC Stage C) that are not eligible for locoregional therapy, surgery or TACE due to tumor size and/or vascular involvement. For these patients, the standard of care for over a decade has been sorafenib (Bayer, A.G.), a oral kinase inhibitor based on the results of a RCT (SHARP study) of 602 patients randomized to sorafenib vs. placebo. Median overall survival (OS) was 10.7 months for sorafenib and 7.9 months for placebo (p\<0.05). The SHARP study included a Western population. A separate study in Asian patients (226 patients from China, South Korea and Taiwan) comparing sorafenib to placebo (Sorafenib-AP study) demonstrated a OS of 6.5 months for sorafenib compared to 4.2 months for placebo (p\<0.05). The placebo OS difference between Asian and Western patients (4.2mo vs 7.9 mo) suggests a difference in the disease characteristics in the Asian population. One significant difference is that the Asian population has an increased prevalence of HBV compared to Western population which may contribute to the increased incidence of HCC and worse OS outcomes observed in Asian patients compared to Western patients. In Thailand and Malaysia sorafenib is not available to a majority of the population presenting with advanced HCC, both due to cost and toxicity profile. This study is designed to evaluate whether AlloStim ® immunotherapy will provide a survival benefit to this population with an improved quality of life compared to approved first line therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
150
3 cycles of intradermal and intravenous administrations
Comparative arm: Physician Choice of FOLFOX4 chemotherapy
Comparative arm: Physician Choice of Sorafenib
Sultan Ismail Hospital
Johor Bahru, Johor, Malaysia
Sultanah Bahiyah Hospital
Alor Star, Kedah, Malaysia
Columbia Asia Bukit Rimau
Shah Alam, Selangor, Malaysia
Siriraj Hospital
Bangkok Noi, Bangkok, Thailand
overall survival
the time from randomization till death
Time frame: rom date of randomization until the date of death from any cause, assessed up to 48 months
Quality of Life Survey
using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep)
Time frame: weekly assessments from baseline to 28 weeks
Time to Symptomatic Progression
To assess time to symptomatic progression (TTSP)
Time frame: rom date of randomization weekly for up to 24 weeks until the date of first documented progression which ever comes first
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Comparative Arm: Physician's Choice of Levantinib
Prince of Songkla University (Songklanagarind Hospital)
Hat Yai, Changwat Songkhla, Thailand
Naresuan University Hospital
Phitsanulok, Tha Pho, Thailand
Chiangmai University
Chiang Mai, Thailand
Songklanagarind Hospital
Khon Kaen, Thailand