AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer
Metastatic Colorectal Cancer
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Cancer Vaccine, AlloStim®, Immunovative, Immunotherapy, Allogeneic Cell Therapy, Cryoablation
Eligibility Criteria
Inclusion Criteria:
- Adult males and female subjects aged 18 years or older at screening visit
- Pathological diagnosis of colorectal adenocarcinoma
Metastatic disease with at least one lesion in liver
- Primary can be intact or resected
- Metastatic lesion(s) in liver non-resectable
- Extrahepatic disease acceptable
- KRAS/BRAF mutant disease or KRAS wild type w/previous anti-EGFR treatment
- At least one liver lesion able to be visualized by ultrasound and determined to be safely assessable for percutaneous cryoablation
Previous treatment failure of at 2 previous lines of active systemic chemotherapy for metastatic disease:
- Previous chemotherapy must have included one line with oxaliplatin (e.g. FOLFOX) and a previous second line with irinotecan (e.g. FOLFIRI) with or without bevacizumab
- If KRAS wild type, at least one anti-EGFR therapy in first or second line
- Treatment failure can be due to disease progression or toxicity
- Disease progression on 2nd line therapy must be documented radiologically and have occurred during or within 30 days following the last administration of 2nd line chemotherapy
- ECOG performance score: 0-1
- Adequate hematological function: Absolute granulocyte count ≥ 1,200/mm3, Platelet count ≥ 100,000/mm3, PT/INR ≤ 1.5 or correctable to <1.5 at time of interventional procedures, Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)
- Adequate Organ Function: Creatinine ≤ 1.5 mg/dL, Total bilirubin ≤ 1.5 times ULN, Alkaline phosphatase ≤ 2.5 times ULN, AST or SGOT ≤ 2.5 times ULN, ALT or SGPT≤2.5 times ULN
- EKG without clinically relevant abnormalities
- Female subjects: Not pregnant or lactating
- Subjects with child bearing potential must agree to use adequate contraception
- Study specific informed consent in the native language of the subject
Exclusion Criteria:
- Peritoneal carcinomatosis
- Moderate or severe ascites requiring medical intervention
- Prior hepatectomy, ablation or chemoembolization of liver lesion
- Prior pelvic radiotherapy
- Clinical or radiological evidence of brain metastasis/leptomeningeal involvement
- Symptomatic asthma or COPD or any lung condition requiring treatment with steroids
- Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment or oxygen saturation <92% on room air
- Bevacizumab (Avastin®) treatment within 6 weeks of scheduled cryoablation
- No Regorafenib prior to or during the Study Period
- Anticoagulant medication for concomitant medical condition (unless can be safely discontinued for invasive cryoablation, biopsy and intratumoral injection procedures)
- 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>5 mg/day of prednisone) within 30 days of the 1st day of study treatment
o Topical corticosteroids are permitted
- Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis). Well controlled Type I diabetes allowed.
- Prior experimental therapy
- History of blood transfusion reactions
- Known allergy to bovine 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
- History of HIV positivity or AIDS
- 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
- History of severe hypersensitivity to monoclonal antibody drugs or any contraindication to any of the study drugs
- Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation
Sites / Locations
- National Cancer Institute of Thailand
Arms of the Study
Arm 1
Arm 2
Experimental
Other
AlloStim® treatment
Physician's Choice (PC)
The treatment schedule includes: (1) the priming step with two ID AlloStim® injections (Days 0 and 3), an additional two ID injections followed by IV infusion of AlloStim® (Days 7 and 10); (2) the vaccination step with cryoablation of a single metastatic lesion followed by injection of AlloStim® into the ablated tumor and IV infusion of AlloStim® on protocol day 14, followed by IV infusion of AlloStim® on Day 17 (3) the activation step with an IV study drug infusion on Day 21 and (4) the booster step with IV booster infusions of AlloStim® on days 49 and 77. Additional booster infusions can be administered monthly at the discretion of the Investigator.
All subjects will be assigned Physician's Choice (PC) therapy. PC can consist of best supportive care (BSC) or any US-FDA-approved cancer drug (e.g. Cetuximab) administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated.