Clinical Trials /

AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer

NCT01741038

Description:

This is a personalized anti-cancer vaccine protocol which includes an in-situ (in the body) cancer vaccine step which combines killing a single metastatic tumor lesion by use of cryoablation in order to cause the release of tumor-specific markers to the immune system and then injecting bioengineered allogeneic immune cells (AlloStim) into the lesion as an adjuvant in order to modulate the immune response and educate the immune system to kill other tumor cells where ever they reside in the body.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer
  • Official Title: A Phase II/III, Randomized, Open Label, Controlled, Two Arm Study Comparing Overall Survival of AlloStim® Combined With Cryoablation to a Physician's Choice Combined With Cryoablation in 3rd Line Treatment for Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: ITL-008-INSTAVAC-CRC
  • NCT ID: NCT01741038

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
AlloStim®AlloStim® treatment

Purpose

This is a personalized anti-cancer vaccine protocol which includes an in-situ (in the body) cancer vaccine step which combines killing a single metastatic tumor lesion by use of cryoablation in order to cause the release of tumor-specific markers to the immune system and then injecting bioengineered allogeneic immune cells (AlloStim) into the lesion as an adjuvant in order to modulate the immune response and educate the immune system to kill other tumor cells where ever they reside in the body.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
AlloStim® treatmentExperimentalThe 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.
  • AlloStim®
Physician's Choice (PC)OtherAll 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.

    Eligibility Criteria

            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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival
    Time Frame:from randomization within 30 days of accrual to death for any cause followed for up to 2 years from date of randomization
    Safety Issue:
    Description:To assess whether cryoablation combined with AlloStim treatment (arm 1) provides an overall survival (OS) advantage when compared to treatment with cryoablation combined with physician's choice (arm 2).

    Secondary Outcome Measures

    Measure:Safety
    Time Frame:168 days from randomization
    Safety Issue:
    Description:Safety will be evaluated by physical exam, changes in laboratory values and patient reported symptoms
    Measure:Health-Related Quality of Life (HRQoL)
    Time Frame:168 days from randomization
    Safety Issue:
    Description:To assess change in HRQoL between treatment arms

    Details

    Phase:Phase 2/Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Immunovative Therapies, Ltd.

    Trial Keywords

    • Cancer Vaccine
    • AlloStim®
    • Immunovative
    • Immunotherapy
    • Allogeneic Cell Therapy
    • Cryoablation

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