An Individualized Anti-Cancer Vaccine in Advanced Hepatocellular Carcinoma Subjects

• Sponsor: Immunovative Therapies, Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02409524
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 32
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Adult Hepatocellular Carcinoma	Biological: AlloVax; Biological: AlloStim; Biological: CRCL	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIA Clinical Study Of An Individualized Anti-Cancer Vaccine (CRCL-ALLOVAX) in Subjects With Advanced Hepatocellular Carcinoma
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. To evaluate survival compared to historical controls [Approximately 12 months]

   Baseline to date of death from any cause

Secondary Outcome Measures

1. To assess AFP as surrogate end-point for response and/or survival [Approximately 6 months]

   Biomarker concentration will be evaluated at different time points

2. To assess mRECIST as surrogate end-point for response and/or survival [Approximately 6 months]

   Objective tumor responses by mRECIST will be compared with OS

3. To evaluate safety in advanced HCC (adverse events) [Approximately 6 months]

   Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events

Other Outcome Measures

1. Anti-Tumor Response [30 days]

   Correlation of radiographic tumor burden assessment (mRECIST) with actual tumor burden determined by histological examination of biopsy samples

2. Tumor-Specific Immunity [30 days]

   Immunological end-points as surrogate markers of response and/or survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Women of child-bearing potential: negative pregnancy test

2. Patients of child producing potential: usage of contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental product

3. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute of Thailand Address: 268/1 Rama Rd. Ratchathewi	Bangkok		Thailand	10400

Sponsors and Collaborators

• Immunovative Therapies, Ltd.

Investigators

• Principal Investigator: Wirote Lausoontornsiri, MD, National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Immunovative Therapies, Ltd.
• ClinicalTrials.gov Identifier: NCT02409524
• Other Study ID Numbers: ITL-022-HCC-BKK-VAX+S
• First Posted: Apr 7, 2015
• Last Update Posted: Jan 22, 2020
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

No Results Posted as of Jan 22, 2020