An Individualized Anti-Cancer Vaccine in Advanced Hepatocellular Carcinoma Subjects

Phase IIA Clinical Study Of An Individualized Anti-Cancer Vaccine (CRCL-ALLOVAX) in Subjects With Advanced Hepatocellular Carcinoma

This is an open-label, single site, Phase IIA clinical trial to investigate the safety and efficacy of an individualized anti-cancer vaccine (CRCL-AlloVax) in advanced HCC patients.

Study Overview

• Status: Completed
• Conditions: Advanced Adult Hepatocellular Carcinoma
• Intervention / Treatment: Biological: AlloStim; Biological: AlloVax; Biological: CRCL

Detailed Description

Hepatocellular carcinoma (HCC) or primary liver cancer is the third leading cause of cancer death worldwide. It accounts for 90% of all liver cancers. More than 80% of patients present with advanced or unresectable disease.

For patients with vascular invasion and/or metastases, the only approved therapy that offers a survival advantage is Sorafenib (Nexavar®). While palliative systemic chemotherapy other than Sorafenib is sometimes offered for HCC, there is no evidence that any chemotherapy has any meaningful therapeutic benefit, especially in overall survival. Subjects in the current study will either have completed at least 90 days of sorafenib treatment or are not able to receive sorafenib due to intolerability or unable to afford. Subjects will continue sorafenib as tolerated while receiving experimental therapy. The experimental dosing schedule has four segments: (1) priming, which consists of intradermal AlloStim alone; (2) vaccination, which consists of intradermal dosing of AlloStim+CRCL; (3) activation, which consists of an intravenous infusion of AlloStim; and (4) booster, which consists of monthly intradermal injections of CRCL alone

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • National Cancer Institute of Thailand Address: 268/1 Rama Rd. Ratchathewi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Males and females who are at least 18 years of age at time of enrollment
2. Histologically confirmed hepatocellular carcinoma with or without positive HBV and/or HCV, not candidate for local regional intervention
3. Minimum of 90 days of sorafenib treatment or ineligible for sorafenib
4. Child-Pugh Stage A-B (score ≥ 5 and ≤ 9)
5. Performance status: ECOG < 2 with no deterioration over the previous 2 weeks
6. Measurable disease (for mRECIST)
7. Lesion amenable for percutaneous tumor harvest and follow up biopsy

8. Adequate bone marrow, liver and renal function as assessed by the following:

   • Hemoglobin > 10.0 g/dl
   • Absolute neutrophil count (ANC) > 1,500/mm3
   • Platelet count > 75,000/μl
   • ALT and AST < 2.5 x ULN
   • Alkaline phosphatase < 4 x ULN
   • Serum creatinine < 1.5
9. Women of child-bearing potential: negative pregnancy test
10. Patients of child producing potential: usage of contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental product
11. 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. Severe ascites, massive or uncontrolled (+3 on Child-Pugh calculator)
2. Severe encephalopathy, uncontrolled (+3 on Child-Pugh calculator)
3. INR > 1.5
4. Participation in another clinical trial evaluating experimental treatments or procedures or receiving medication/treatment for HCC other than sorafenib
5. Any autoimmune disorder
6. Any clinical condition requiring systemic steroids or current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 1 month of study entry
7. HIV positive or syphilis
8. History of cardiac disease: congestive heart failure > NYHA class 2; cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted) or uncontrolled hypertension
9. Active clinically serious infections (> grade 2 NCI-CTCAE version 4.0)
10. History of organ or tissue allograft
11. Advanced liver cirrhosis
12. Interferon or thalidomide within 1 month prior to signing informed consent
13. Uncontrolled concurrent serious medical or psychiatric illness
14. Clinically apparent central nervous system metastases or carcinomatous meningitis
15. History of blood transfusion reactions
16. Known allergy to murine monoclonal antibodies or bovine products or cow milk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment; The treatment schedule of AlloVax includes: (1) Priming segment with ID injections of AlloStim on Days 0, 3, 7 and 10. (2) Vaccination segment with ID injections of AlloStim+CRCL on Days 14, 17, 21 and 24. (3) Activation segment with IV push infusion of AlloStim on Day 28. (4) Booster Segment with monthly (every 28 days) ID injections of CRCL alone beginning on Day 56. These injections will continue until all the vaccine is used or the death of the subject

Biological: AlloStim; AlloStim (ID) injection AlloStim (IV) infusion; Other Names: AlloStim ID; AlloStim IV; Biological: AlloVax; Personalized anti-cancer vaccine (injection of AlloStim followed immediately by the injection of CRCL); Other Names: CRCL and AlloStim; Biological: CRCL; Autologous tumor-derived chaperone protein mixture; Other Names: Chaperone Rich Cell Lysate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate survival compared to historical controls	Baseline to date of death from any cause	Approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess AFP as surrogate end-point for response and/or survival	Biomarker concentration will be evaluated at different time points	Approximately 6 months
To assess mRECIST as surrogate end-point for response and/or survival	Objective tumor responses by mRECIST will be compared with OS	Approximately 6 months
To evaluate safety in advanced HCC (adverse events)	Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events	Approximately 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Tumor Response	Correlation of radiographic tumor burden assessment (mRECIST) with actual tumor burden determined by histological examination of biopsy samples	30 days
Tumor-Specific Immunity	Immunological end-points as surrogate markers of response and/or survival	30 days

Collaborators and Investigators

• Sponsor: Immunovative Therapies, Ltd.
• Investigators: Principal Investigator: Wirote Lausoontornsiri, MD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2016
• Primary Completion (ACTUAL): June 1, 2017
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 6, 2015
• First Posted (ESTIMATE): April 7, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 17, 2020
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: ITL-022-HCC-BKK-VAX+S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO