Clinical Trials /

Immunotherapy for Third Line Metastatic Colorectal Cancer

NCT04444622

Description:

This is a Phase IIB multi-site, open label study of a next generation immunotherapy for third-line MSI-S metastatic colorectal cancer using an "off-the-shelf", non-genetically manipulated living immune cell product (AlloStim) derived from the blood of healthy donors.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Immunotherapy for Third Line Metastatic Colorectal Cancer
  • Official Title: Phase IIB Open-Label Study to Assess the Safety and Efficacy of STIMVAX® as Third-line Therapy for Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: ITL-032-MCRC3-STIM
  • NCT ID: NCT04444622

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
AlloStimStimVaxAlloStim

Purpose

This is a Phase IIB multi-site, open label study of a next generation immunotherapy for third-line MSI-S metastatic colorectal cancer using an "off-the-shelf", non-genetically manipulated living immune cell product (AlloStim) derived from the blood of healthy donors.

Detailed Description

      This is a Phase IIB open label immunotherapy protocol called "StimVax". The protocol design
      is based upon information obtained from a previous Phase IIA dose level and dose frequency
      ranging study. The population targeted is MSI-S metastatic colorectal cancer previously
      treated with two lines of chemotherapy regimens, one containing oxaliplatin and the other
      containing irinotecan. This population is not considered to be responsive to immunotherapy.

      The study drug is called "AlloStim". AlloStim is an "off-the-shelf",
      non-genetically-manipulated, living immune cell immunotherapy. AlloStim is derived from
      precursors purified from the blood of healthy donors and grown and differentiated in
      specialized bioreactors in the laboratory. Because the donors are intentionally mis-matched
      to the host, AlloStim is completely eliminated by the host in a non-toxic rejection response
      within 24h of administration.

      Unlike autologous immune cell therapies, like CAR-T cells or TIL cells, AlloStim is
      allogeneic and is not intended to directly kill tumors. Rather, the novel AlloStim mechanism
      is designed to modify and train the host immune system to kill tumors and prevent tumor
      growth and spread. Uniquely, the AlloStim mechanism is also designed to increase Th1/Th2
      balance, activate innate effector cells (such as NK and NKT), counter-regulate the immune
      suppressive and immune evasion mechanisms that tumors use to evade immune elimination both
      systemically and in the tumor microenvironment.

      The AlloStim mechanism creates self-amplifying waves of temporal and spatial immune effects
      that can lead to an initial non-specific cellular innate NK cell immune response followed by
      a tumor-specific killer T-cell immune response specific for the host tumor through a
      combination of immune processes called "allo-priming" and "in-situ vaccination".
    

Trial Arms

NameTypeDescriptionInterventions
AlloStimExperimentalAlloStim is administered in three cycles: Cycle 1 Day 0: 0.5ml ID AlloStim® Day 7: 0.5ml ID AlloStim® Day 14: 0.5ml ID AlloStim® Day 21: 0.5ml ID AlloStim® Day 28: 0.5ml ID AlloStim® Cycle 2 Day 42: 0.5ml ID AlloStim® Day 49: 0.5ml ID AlloStim® Day 56: 0.5ml ID AlloStim® Day 63: 0.5ml ID AlloStim® Day 70: 0.5ml ID AlloStim® + 3ml IV AlloStim® Cycle 3 Day 84: 0.5ml ID AlloStim® Day 91: 0.5ml ID AlloStim® Day 98: 0.5ml ID AlloStim® Day 105: 0.5ml ID AlloStim® Day 112: 0.5ml ID AlloStim® + 3ml IV AlloStim®
  • AlloStim

Eligibility Criteria

        Inclusion Criteria:

          1. Adult males and female subjects aged 18-80 years at screening visit

          2. Pathologically confirmed diagnosis of colorectal adenocarcinoma

          3. Presenting with metastatic disease:

               -  Primary can be intact or previously resected

               -  Preferably with metastasis to the liver or other location for safe percutaneous
                  biopsy

          4. Previous treatment failure of two previous lines of active systemic chemotherapy:

               -  Previous chemotherapy must have included an oxaliplatin-containing (e.g. FOLFOX)
                  and an irinotecan-containing (e.g. FOLFIRI) regimen

               -  With or without bevacizumab

               -  Administered in adjuvant setting or for treatment of metastatic disease

               -  If KRAS wild type, must have at least one prior anti-EGFR therapy

               -  Treatment failure can be due to disease progression or toxicity

               -  Disease progression on second line therapy must be documented radiologically and
                  must have occurred during or within 30 days following the last administration of
                  treatment for metastatic disease

          5. ECOG performance score: 0-1

          6. 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)

          7. Adequate Organ Function:

               -  Creatinine ≤ 1.5 mg/dL

               -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

               -  Alkaline phosphatase ≤ 2.5 times ULN *

               -  Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN *

               -  Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN * *or ≤5x ULN if liver
                  involvement

          8. EKG without clinically relevant abnormalities

          9. Female subjects: Not pregnant or lactating

         10. Patients with child bearing potential must agree to use adequate contraception

         11. Study specific informed consent in the native language of the subject.

        Exclusion Criteria:

          1. high frequency microsatellite instability (MSI-H)

          2. Bowel obstruction or high risk for obstruction if tumors become inflamed

          3. Moderate or severe ascites requiring medical intervention

          4. Clinical evidence or radiological evidence of brain metastasis or leptomeningeal
             involvement

          5. Peritoneal carcinomatosis

          6. Symptomatic asthma or COPD

          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 baseline scheduled biopsy procedure

          9. Any of the following mood disorders: active major depressive episode, history of
             suicidal attempt or ideation

         10. Prior allogeneic bone marrow/stem cell or solid organ transplant

         11. 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 first day of study
             drug treatment

               -  Topical corticosteroids are permitted

         12. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple
             sclerosis, autoimmune thyroid disease, uveitis).

               -  Well controlled Type I diabetes allowed

         13. Prior experimental therapy

         14. History of blood transfusion reactions

         15. Progressive viral or bacterial infection

               -  All infections must be resolved and the subject must remain afebrile for seven
                  days without antibiotics prior to being placed on study

         16. Cardiac disease of symptomatic nature

         17. History of HIV positivity or AIDS

         18. 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 biopsy procedures

         19. History of severe hypersensitivity to monoclonal antibody drugs

         20. Psychiatric or addictive disorders or other condition that, in the opinion of the
             investigator, would preclude study participation.

         21. Subjects that lack ability to provide consent for themselves.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:date of death from any cause, whichever came first, assessed up to 12 months from accrual
Safety Issue:
Description:measurement of the survival on experimental treatment

Details

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

Trial Keywords

  • immunotherapy
  • cancer vaccine
  • colorectal cancer
  • AlloStim
  • MSI-S

Last Updated

June 22, 2020