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Immunotherapy for Third Line Metastatic Colorectal Cancer (STIMVAX)

Primary Purpose

Metastatic Colorectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AlloStim
Sponsored by
Immunovative Therapies, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring immunotherapy, cancer vaccine, colorectal cancer, AlloStim, MSI-S

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mt. Sinai Comprehensive Cancer CenterRecruiting
  • Karmanos Cancer InstituteRecruiting
  • Summit HealthRecruiting
  • Hirschfield Oncology CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AlloStim

Arm Description

AlloStim 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®

Outcomes

Primary Outcome Measures

Overall Survival
measurement of the survival on experimental treatment
Incidents of Adverse Events (AE)
to evaluate safety and tolerability

Secondary Outcome Measures

Full Information

First Posted
June 19, 2020
Last Updated
July 25, 2023
Sponsor
Immunovative Therapies, Ltd.
Collaborators
Mirror Biologics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04444622
Brief Title
Immunotherapy for Third Line Metastatic Colorectal Cancer
Acronym
STIMVAX
Official Title
Phase IIB Open-Label Study to Assess the Safety and Efficacy of STIMVAX® as Third-line Therapy for Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2021 (Actual)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immunovative Therapies, Ltd.
Collaborators
Mirror Biologics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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".

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
immunotherapy, cancer vaccine, colorectal cancer, AlloStim, MSI-S

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AlloStim
Arm Type
Experimental
Arm Description
AlloStim 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®
Intervention Type
Biological
Intervention Name(s)
AlloStim
Other Intervention Name(s)
StimVax
Intervention Description
Living bioengineered, non-genetically manipulated, activated Th1-like immune cells differentiated and expanded from precursor cells purified from blood of healthy unrelated donors
Primary Outcome Measure Information:
Title
Overall Survival
Description
measurement of the survival on experimental treatment
Time Frame
date of death from any cause, whichever came first, assessed up to 12 months from accrual
Title
Incidents of Adverse Events (AE)
Description
to evaluate safety and tolerability
Time Frame
day 0 to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult males and female subjects aged 18-80 years at screening visit Pathologically confirmed diagnosis of colorectal adenocarcinoma Presenting with metastatic disease: 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 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 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 EKG without clinically relevant abnormalities Female subjects: Not pregnant or lactating Patients with child bearing potential must agree to use adequate contraception Study specific informed consent in the native language of the subject. Exclusion Criteria: high frequency microsatellite instability (MSI-H) Bowel obstruction or high risk for obstruction if tumors become inflamed Moderate or severe ascites requiring medical intervention Clinical evidence or radiological evidence of brain metastasis or leptomeningeal involvement Peritoneal carcinomatosis Symptomatic asthma or COPD 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 baseline scheduled biopsy procedure Any of the following mood disorders: active major depressive episode, history of suicidal attempt or ideation 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 first day of study drug treatment 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 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 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 biopsy procedures History of severe hypersensitivity to monoclonal antibody drugs Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation. Subjects that lack ability to provide consent for themselves.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kim Demonte
Phone
732-630-9059
Email
axellaresearch@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Thu Bui, MHA
Phone
619-227-4872
Email
thu@immunovative.com
Facility Information:
Facility Name
Mt. Sinai Comprehensive Cancer Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luz Smith
Phone
305-674-2625
Email
Luz.Smith@msmc.com
First Name & Middle Initial & Last Name & Degree
Mike Cusnir, MD
First Name & Middle Initial & Last Name & Degree
Oleg Gligich, MD
First Name & Middle Initial & Last Name & Degree
Gerard Chaaya, MD
First Name & Middle Initial & Last Name & Degree
Jacqueline Barrientos, MD
First Name & Middle Initial & Last Name & Degree
Ragisha Gopalakrishnan, MD
First Name & Middle Initial & Last Name & Degree
Aron Simkins, MD
First Name & Middle Initial & Last Name & Degree
Michael Schwartz, MD
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prachi Shah
Phone
313-576-9382
Email
shahp@karmanos.org
First Name & Middle Initial & Last Name & Degree
Paige Buzenski
Phone
313-576-9380
Email
buzenskp@karmanos.org
First Name & Middle Initial & Last Name & Degree
Mohammed Al Hallak, MD
Facility Name
Summit Health
City
Florham Park
State/Province
New Jersey
ZIP/Postal Code
07932
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Mackenzie, RN
Phone
973-436-1752
Email
mmackenzie@summithealth.com
First Name & Middle Initial & Last Name & Degree
David Gallinson, MD
Facility Name
Hirschfield Oncology Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karla Witkowski
Phone
718-732-4050
Email
karla@honcology.com
First Name & Middle Initial & Last Name & Degree
Azriel Hirschfeld, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
18054441
Citation
Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.
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Immunotherapy for Third Line Metastatic Colorectal Cancer

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