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.

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

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