A Phase I/II Study of an Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancers
A Phase I/II Study of an Experimental Therapeutic Cancer Vaccine Created In-situ in Patients With Stage II-Stage IV Cancers
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.
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.
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