In-Situ Therapeutic Cancer Vaccine for Metastatic Cancer Combining AlloStim With Tumor Cryoablation

June 6, 2011 updated by: Immunovative Therapies, Ltd.

Phase I/II Study of a Therapeutic Cancer Vacccine Created In-situ in Patients With Refractory or Metastatic Cancer

This is a Phase I/II study to investigate the feasibility of creating a personalized therapeutic cancer vaccine within the body. A vaccine contains a source of tumor antigen and an adjuvant. In this study, tumor antigen is generated by freezing a tumor by a minimally invasive percutaneous (through the skin) cryoablation procedure. The study drug, AlloStim, is injected into the ablated tumor to promote development of an anti-tumor immune response.

Study Overview

Status

Completed

Conditions

Metastatic Cancer

Intervention / Treatment

Detailed Description

This is a Phase I/II clinical study to investigate the feasibility of creating a personalized anti-tumor vaccine within the body of patients with advanced cancers. The aim of the study is to evaluate the safety of administration and anti-tumor effect of a vaccine protocol that has three separate phases. Cancer patients generally present with an immune response to cancer biased to a Th2 response, while a Th1 response is considered necessary for mediating anti-tumor immunity. The first step of the study consists of three (3) weekly intradermal priming doses of AlloStim. The aim of this step is to create Th1 immunity to the alloantigens in AlloStim, thus increasing the number of Th1 cells in circulation. The second step of the protocol involves the cryoablation of a selected tumor lesion followed by an intratumoral AlloStimTM injection. The aim of this step is to generate tumor-specific CTL killer cells in the circulation. The final step is an intravenous infusion of AlloStim. The aim of this step is to activate circulating Th1 cells, killer cells, and natural killer cells The further aim of this step is to create an inflammatory environment that can break-down the ability of the tumor to avoid an anti-tumor immune response.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2
Phase 1

Contacts and Locations

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

Study Locations

United States
- California
  - Carlsbad, California, United States, 92010
    - Immunovative Clinical Research, Inc

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

18 years or older
Metastatic cancer refractory to at least one course of active chemotherapy or prior radiation therapy, including metastatic breast cancer, colorectal cancer, non-small cell lung cancer, ovarian or other gynecological cancer, prostate cancer, pancreatic or other GI cancer, melanoma, head or neck cancer or lymphoma/plasmacytoma.
Measurable disease determined upon review of abdominal and/or chest CT scan within 60 days of evaluation for study inclusion with a target tumor lesion for cryoablation located in liver, kidney, bone, pancreas, lymph node, skin, neck or prostate deemed to be accessible for percutaneous access.
Acceptable cryoablation procedure technique risk: the target tumor for ablation must have adequate distance from adjacent vasculature and other organs to permit safe application of cryoprobe (generally, more than a 2.5cm clearance of the cryoprobe from any vital structure such as the bowel, inferior vena cava, or aorta). The safety assessment of the cryoprobe placement will be made an attending radiologist based on imaging studies.
Life expectancy >180 days
No bevacizumab (Avastin®) within 6 weeks of planned cryoablation procedure
ECOG status 0-1
No concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to cryoablation procedure
No low molecular weight heparin preparations unless can be discontinued 8 hours prior to cryoablation
At least 2 weeks since prior cytotoxic chemotherapy
Absolute granulocyte count ≥ 1,200/mm3
Platelet count ≥ 100,000/mm3
PT/INR ≤ 1.5
- INR correctable to ≤ 1.5 or a PT/PTT correctable to normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be monitored weekly prior to the cryoablation day 21 to assure INR is stable. However, heparin or warfarin must be withheld prior to cryoablation such that the above criteria are met.
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 1.5 mg/dL
Total bilirubin ≤ 1.5 times normal
Alkaline phosphatase ≤ 2.5 times normal (≤ 5 times normal if liver involvement)
Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN
Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN
Not pregnant or lactating
Patients with child bearing potential must agree to use adequate contraception
No psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation
Study specific informed consent

Exclusion Criteria:

Taking anticoagulant medication for concomitant medical condition (unless can be safely discontinued for cryoablation procedure)
Prior allogeneic bone marrow/stem cell or solid organ transplant
Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of study drug treatment
- Topical and inhaled corticosteroids are permitted
Concomitant autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)
Prior experimental cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine)
Immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 3 months of study entry

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: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
evaluation of any drug-related toxicity associated with AlloStim administration as well as the reversibility of such toxicity. Time Frame: 90 days	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
evaluation of the anti-tumor effect of AlloStim administration Time Frame: 90 days	90 days
evaluation of the immunological response to AlloStim administration Time Frame: 90 days	90 days

Collaborators and Investigators

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

Sponsor

Immunovative Therapies, Ltd.

Investigators

Study Director: Dr. Michael Har-Noy, Immunovative Therapies, Ltd.
Principal Investigator: Michael Berger, MD, Immunotherapy Clinical Associates, PC

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.

General Publications

Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.

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

August 1, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

March 12, 2009

First Submitted That Met QC Criteria