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:

Not yet recruiting

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.
    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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