An Individualized Anti-Cancer Vaccine in Advanced Hepatocellular Carcinoma Subjects

Study Overview
=================
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.

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

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

Conditions
-----------------
Advanced Adult Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Biological: AlloVax
* Biological: AlloStim
* Biological: CRCL


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Males and females who are at least 18 years of age at time of enrollment Histologically confirmed hepatocellular carcinoma with or without positive HBV and/or HCV, not candidate for local regional intervention Minimum of 90 days of sorafenib treatment or ineligible for sorafenib Child-Pugh Stage A-B (score ≥ 5 and ≤ 9) Performance status: ECOG < 2 with no deterioration over the previous 2 weeks Measurable disease (for mRECIST) Lesion amenable for percutaneous tumor harvest and follow up biopsy 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 Women of child-bearing potential: negative pregnancy test Patients of child producing potential: usage of contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental product Ability to understand the study, its inherent risks, side effects and potential benefits and ability to give written informed consent to participate Exclusion criteria: Severe ascites, massive or uncontrolled (+3 on Child-Pugh calculator) Severe encephalopathy, uncontrolled (+3 on Child-Pugh calculator) INR > 1.5 Participation in another clinical trial evaluating experimental treatments or procedures or receiving medication/treatment for HCC other than sorafenib Any autoimmune disorder Any clinical condition requiring systemic steroids or current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 1 month of study entry HIV positive or syphilis 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 Active clinically serious infections (> grade 2 NCI-CTCAE version 4.0) History of organ or tissue allograft Advanced liver cirrhosis Interferon or thalidomide within 1 month prior to signing informed consent Uncontrolled concurrent serious medical or psychiatric illness Clinically apparent central nervous system metastases or carcinomatous meningitis History of blood transfusion reactions Known allergy to murine monoclonal antibodies or bovine products or cow milk

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>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<br>* Personalized anti-cancer vaccine (injection of AlloStim followed immediately by the injection of CRCL)<br>* Other names: CRCL and AlloStim;Biological: AlloStim<br>* AlloStim (ID) injection AlloStim (IV) infusion<br>* Other names: AlloStim IV;Biological: CRCL<br>* Autologous tumor-derived chaperone protein mixture<br>* 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 |