Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancer

This study has been withdrawn prior to enrollment.
(Protocol withdrawn for lack of financial support)
Sponsor:
Collaborator:
Hadassah Medical Organization
Information provided by:
Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier:
NCT01065441
First received: February 7, 2010
Last updated: November 29, 2012
Last verified: May 2011
  Purpose

A Phase I/II study of an in-situ therapeutic cancer vaccine. Vaccines contain a source of antigen and and adjuvant. In this study the source of tumor antigen comes from the killing of a selected tumor by cryoablation (killing using extreme cold) and the adjuvant is intentionally mis-matched immune cells (AlloStim-TM) engineered to produce inflammatory cytokines.


Condition Intervention Phase
Solid Tumors Stage II, Stage III and Stage IV
Breast Cancer
Colorectal Cancer
Prostate Cancer
Melanoma
Ovarian Cancer
Sarcoma
Non-small Cell Lung Cancer
Biological: AlloStim
Procedure: Cryoablation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of an Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancers

Resource links provided by NLM:


Further study details as provided by Immunovative Therapies, Ltd.:

Primary Outcome Measures:
  • The primary endpoint is the evaluation of any drug-related toxicity associated with AlloStimTM administration as well as the reversibility of such toxicity. [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary end-point is the evaluation of the anti-tumor effect of AlloStimTM administration. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The tertiary end-point is the evaluation of the immunological response to AlloStim-TM administration. [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: December 2009
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: AlloStim
    Patients meeting eligibility criteria will be primed with at least three and up to nine intradermal AlloStim-TM injections at a frequency of every 2-8 days at doses between 1-4 x 10^7 cells
    Procedure: Cryoablation
    Percutaneous cryoablation of selected tumor lesion under CT or US guidance
    Biological: AlloStim
    intratumoral injection of AlloStim-TM into cryoablated tumor lesion at a dose of 1-6 x 10^7 cells
    Biological: AlloStim
    intravenous AlloStim-TM at doses between 1 x 10^7 to 1 x 10^9 cells
    Biological: AlloStim
    Intraperitoneal AlloStim-TM infusion in patients with peritoneal carcinomatosis and/or ascites
    Biological: AlloStim
    Patients with malignant pleural effusion may receive intrapleural AlloStim-TM infusion at a dose of 5-10 x 10^7 cells.
    Biological: AlloStim
    Patients with palpable tumors may receive alcohol ablation and intratumoral AlloStim-TM
Detailed Description:

This is a Phase I/II clinical study to investigate the optimal protocol and indication for creating a personalized anti-tumor vaccine within the body of patients with cancer. The aim of the study is to evaluate the safety of administration and anti-tumor effect of a vaccine protocol that has three separate steps. 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 multiple intradermal priming doses of AlloStimTM. The aim of this step is to create Th1 immunity to the alloantigens in AlloStimTM, 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 AlloStimTM. 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. In patients with partial responses and recurrence of disease, additional intravenous "booster" infusions are utilized to reactivate the circulating immune cells.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years or older
  • Stage II-IV including 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 or alcohol ablation located in liver, kidney, bone, lung, adrenal, pancreas, lymph node, skin, neck or prostate deemed to be accessible for percutaneous access or carcinomatosis or malignant ascites or malignant pleural effusion.
  • When applicable, 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 >90 days
  • No bevacizumab (Avastin®) within 6 weeks of planned cryoablation procedure
  • ECOG status 0-2
  • 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

    o 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 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

    o Topical and inhaled corticosteroids are permitted

  • Concomitant active 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
  • History of blood transfusion reactions
  • Known allergy to bovine products
  • Know allergy to murine products
  • Progressive viral or bacterial infection

    o All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed on study

  • Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%
  • Symptomatic pulmonary disease or FEV1, FVC, and DLCO ≤ 50% predicted
  • History of HIV positivity or AIDS o HBV and/or HCV positivity is permitted
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01065441

Locations
Israel
Hadassah-Hebrew University Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Immunovative Therapies, Ltd.
Hadassah Medical Organization
Investigators
Principal Investigator: Tamar Peretz, MD Hadassah Medical Organization
Study Chair: Dr. Michael Har-Noy Immunovative Therapies, Ltd.
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Michael Har-Noy, Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier: NCT01065441     History of Changes
Other Study ID Numbers: ITL-002-HMC
Study First Received: February 7, 2010
Last Updated: November 29, 2012
Health Authority: Israel: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Immunovative Therapies, Ltd.:
breast cancer
colorectal cancer
prostate cancer
melanoma
ovarian cancer
GI cancer
Sarcoma
Renal Cell Carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Lung Neoplasms
Melanoma
Ovarian Neoplasms
Prostatic Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 28, 2014