Immunotherapy for Advanced Liver Cancer (ALIVE)

March 4, 2024 updated by: Immunovative Therapies, Ltd.

Phase II/III Randomized, Controlled Clinical Study of AlloStim(R) vs Physician's Choice in Asian Subjects With Advanced Hepatocellular Carcinoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

150

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Malaysia
    • George Town
      • Pulau Pinang, George Town, Malaysia, 10990
        • Not yet recruiting
        • Hospital Pulau Pinang
        • Contact:
        • Principal Investigator:
          • Heng Chin Fong, MD
    • Johor
      • Johor Bahru, Johor, Malaysia, 81100
        • Recruiting
        • Sultan Ismail Hospital
        • Contact:
        • Principal Investigator:
          • Sen Chun Lim, MD
    • Kedah
      • Alor Setar, Kedah, Malaysia, 05460
        • Recruiting
        • Sultanah Bahiyah Hospital
        • Contact:
        • Principal Investigator:
          • Datuk Dr Muhammad Radzi Abu Hassan, MD
    • Selangor Darul Ehsan
      • Shah Alam, Selangor Darul Ehsan, Malaysia, 40460
        • Recruiting
        • Columbia Asia Bukit Rimau
        • Contact:
        • Principal Investigator:
          • Kananathan Ratnavelu, MD
        • Sub-Investigator:
          • Dharmaratnam Jeyandran, MD
  • Thailand
    • Bangkok
      • Bangkok Noi, Bangkok, Thailand, 10700
        • Recruiting
        • Siriraj Hospital
        • Contact:
        • Principal Investigator:
          • Krittiya Korphaisarn, MD
      • Ratchathewi, Bangkok, Thailand, 10400
        • Recruiting
        • Ramathibodi hospital
        • Contact:
        • Principal Investigator:
          • Abhasnee Sobhonslidsuk, MD
    • Songkhla
      • Hat Yai, Songkhla, Thailand, 90110
        • Recruiting
        • Prince of Songkla University (Songklanagarind Hospital)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Arunee Dechaphunkul, MD
    • Tha Pho
      • Phitsanulok, Tha Pho, Thailand, 65000
        • Recruiting
        • Naresuan University Hospital
        • Contact:
        • Principal Investigator:
          • Ekawee Sripariwuth, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Males and females who are at least 18 years of age at time of enrollment
  2. Histologically or cytologically documented advanced HCC (BCLC stage C) disease at diagnosis.
  3. No prior treatment for BCLC class C disease.
  4. Child-Pugh Class A or subset of Child-Pugh Class B
  5. Performance status: ECOG < 2 with no deterioration over the previous 2 weeks
  6. With or without positive HBV and/or HCV
  7. With or without extrahepatic disease and with or without macrovascular invasion
  8. Measurable enhancing disease in liver with at least one target lesion evaluable by mRECIST

  9. Adequate hematological, liver and renal function as assessed by the following:

    • Hemoglobin > 10.0 g/dl
    • Platelet count > 75,000/μl
    • ALT and AST < 5.0 x ULN
    • Serum creatinine < 1.5
  10. Women of child-bearing potential: negative pregnancy test
  11. Patients of child producing potential: usage of contraception or avoidance of pregnancy measures while enrolled on study
  12. Ability to understand the study, its inherent risks, side effects and potential benefits and ability to give written informed consent to participate

Exclusion Criteria:

  1. Any prior cancer diagnosis (other than cured basal cell carcinoma, head and neck carcinoma in-situ, or superficial Ta, Tis, T1 bladder cancer) or concurrent cancer histologically different than HCC (e.g., cholangiocarcinoma).
  2. Child-Pugh liver function combined score >9 (Class C or Class D)
  3. Moderate uncontrolled or severe ascites (+3 on Child-Pugh calculator)
  4. Clinical symptoms of hepatic decompensation or presence of hepatic encephalopathy
  5. Severe stomach/esophageal varices requiring interventional treatment.
  6. Unable to tolerate radiological contrast dye
  7. Any prior experimental, approved or off-label treatment for HCC (including levantinib, nivolumab, duvalumab, tremelimumab, brivananib, cabozantinib or ramucircumab) or any approved or experimental procedures such as surgery, radiation or ablation.
  8. Enrollment in any previous clinical trial for HCC
  9. Any history of autoimmune disorder (type I, insulin-dependent diabetes allowed)
  10. History of COPD or oxygen saturation <92% at room air
  11. Any clinical condition requiring systemic steroids (inhaled steroids allowed) or any current immunosuppressive therapy or anti-epileptic drug therapy.
  12. Known history of HIV infection
  13. Clinically significant gastrointestinal bleeding within 30 days prior to study entry
  14. History of cardiac disease: congestive heart failure > NYHA class 2; cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted)
  15. Uncontrolled hypertension (SBP >150 or DBP>90).
  16. Active clinically serious infections (> grade 2 CTCAE version 5.0)
  17. History of organ transplant or tissue allograft
  18. Uncontrolled concurrent serious medical or psychiatric illness
  19. Clinically apparent central nervous system metastases or carcinomatous meningitis
  20. History of drug abuse or current alcohol abuse
  21. History of blood transfusion reactions
  22. Pregnant or lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AlloStim®
AlloStim® is a formulation of living allogeneic Th1-like cells with anti-CD3/CD28 microbeads attached derived from precursors purified from healthy screened blood donors that are differentiated and expanded ex-vivo. AlloStim® is formulated at 10-7 cells/ml in 0.5ml for ID administration and 3ml for IV administration
Biological: AlloStim® immunotherapy
3 cycles of intradermal and intravenous administrations
Active Comparator: Physician's Choice
Physician's Choice is sorafenib or levantinib or FOLFOX4 monotherapy
Drug: FOLFOX regimen
Comparative arm: Physician Choice of FOLFOX4 chemotherapy
Other Names:
  • Physician Choice FOLFOX4
Drug: Sorafenib
Comparative arm: Physician Choice of Sorafenib
Other Names:
  • Sorafenib Physician's Choice
Drug: Lenvatinib
Comparative Arm: Physician's Choice of Levantinib
Other Names:
  • Levantinib Physician's Choice

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: rom date of randomization until the date of death from any cause, assessed up to 48 months
the time from randomization till death
rom date of randomization until the date of death from any cause, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life Survey
Time Frame: weekly assessments from baseline to 28 weeks
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)
weekly assessments from baseline to 28 weeks
Time to Symptomatic Progression
Time Frame: rom date of randomization weekly for up to 24 weeks until the date of first documented progression which ever comes first
To assess time to symptomatic progression (TTSP)
rom date of randomization weekly for up to 24 weeks until the date of first documented progression which ever comes first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immunovative Therapies, Ltd.

Collaborators

Mirror Biologics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

August 25, 2021

First Submitted That Met QC Criteria

August 30, 2021

First Posted (Actual)

September 2, 2021

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MBI-003-LIVE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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