Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Metastasis is the
main reason of death in CRC patients. The current drugs used to treat colorectal cancer
provide important treatment options for patients, their limitations including drug
resistance, poor efficacy and severe side effects. Development of new therapeutic strategies
for KRAS mutant as well as BRAF mutant tumors are therefore highly needed in order to offer a
new category of drug (immunotherapy). This study targets the population of mCRC patients that
have progressed after two lines of chemotherapy and are not eligible for targeted therapies
due to a mutation in KRAS or BRAF.
This is a Phase II/III, randomized, open-label, multicenter, controlled, two arm study
designed to determine the efficacy in terms of OS and the safety of the InSituVax (AlloStim+
Cryoablation) personalized in-situ anti-cancer vaccine protocol (Treatment Arm) compared with
Physician's Choice (PC) of Treatment + Cryoablation (Control Arm) in Metastatic Colorectal
Cancer. Subjects are randomized 2:1 into the treatment or control arms.
Inclusion Criteria:
1. Adult males and female subjects aged 18 years or older at screening visit
2. Pathological diagnosis of colorectal adenocarcinoma
3. 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
4. KRAS/BRAF mutant disease or KRAS wild type w/previous anti-EGFR treatment
5. At least one liver lesion able to be visualized by ultrasound and determined to be
safely assessable for percutaneous cryoablation
6. 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
7. ECOG performance score: 0-1
8. 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)
9. 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
10. EKG without clinically relevant abnormalities
11. Female subjects: Not pregnant or lactating
12. Subjects with child bearing potential must agree to use adequate contraception
13. Study specific informed consent in the native language of the subject
Exclusion Criteria:
1. Peritoneal carcinomatosis
2. Moderate or severe ascites requiring medical intervention
3. Prior hepatectomy, ablation or chemoembolization of liver lesion
4. Prior pelvic radiotherapy
5. Clinical or radiological evidence of brain metastasis/leptomeningeal involvement
6. Symptomatic asthma or COPD or any lung condition requiring treatment with steroids
7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in
pulmonary dysfunction requiring active treatment or oxygen saturation <92% on room air
8. Bevacizumab (Avastin®) treatment within 6 weeks of scheduled cryoablation
9. No Regorafenib prior to or during the Study Period
10. Anticoagulant medication for concomitant medical condition (unless can be safely
discontinued for invasive cryoablation, biopsy and intratumoral injection procedures)
11. Prior allogeneic bone marrow/stem cell or solid organ transplant
12. 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
13. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple
sclerosis, autoimmune thyroid disease, uveitis). Well controlled Type I diabetes
allowed.
14. Prior experimental therapy
15. History of blood transfusion reactions
16. Known allergy to bovine products
17. 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
18. Cardiac disease of symptomatic nature
19. History of HIV positivity or AIDS
20. 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
21. History of severe hypersensitivity to monoclonal antibody drugs or any
contraindication to any of the study drugs
22. Psychiatric or addictive disorders or other condition that, in the opinion of the
investigator, would preclude study participation
