Clinical Trials /

VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

NCT03373188

Description:

This randomized phase I trial studies how well anti-semaphorin 4D (anti-SEMA4D) monoclonal antibody VX15/2503 with or without ipilimumab or nivolumab work in treating patients with stage I-III pancreatic cancer that can be removed by surgery or stage IV colorectal cancer that has spread to the liver and can be removed by surgery. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Colorectal Carcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer
  • Official Title: Phase I Integrated Biomarker Trial of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Pancreatic and Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00098707
  • SECONDARY ID: NCI-2017-01618
  • SECONDARY ID: Winship4142-17
  • NCT ID: NCT03373188

Conditions

  • Colon Carcinoma Metastatic in the Liver
  • Colorectal Adenocarcinoma
  • Pancreatic Adenocarcinoma
  • Resectable Pancreatic Carcinoma
  • Stage I Pancreatic Cancer
  • Stage IA Pancreatic Cancer
  • Stage IB Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage IIA Pancreatic Cancer
  • Stage IIB Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Stage IV Colorectal Cancer
  • Stage IVA Colorectal Cancer
  • Stage IVB Colorectal Cancer

Interventions

DrugSynonymsArms
Anti-SEMA4D Monoclonal Antibody VX15/2503moAb VX15/2503, VX15/2503Arm II (VX15/2503, surgery)
IpilimumabBMS-734016, MDX-010, MDX-CTLA4, YervoyArm III (VX15/2503, ipilimumab, surgery)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm IV (VX15/2503, nivolumab, surgery)

Purpose

This randomized phase I trial studies how well anti-semaphorin 4D (anti-SEMA4D) monoclonal antibody VX15/2503 with or without ipilimumab or nivolumab work in treating patients with stage I-III pancreatic cancer that can be removed by surgery or stage IV colorectal cancer that has spread to the liver and can be removed by surgery. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVE:

      To evaluate the effect of the anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) alone and
      VX15/2503 in combination with immune checkpoint inhibitors, ipilimumab or nivolumab, on the
      immune profile in the tumor microenvironment and in peripheral blood.

      SECONDARY OBJECTIVE:

      To extend the previously reported safety profile of single agent VX15/2503 to the combination
      of VX15/2503 and immune checkpoint inhibitors, ipilimumab or nivolumab, in patients with
      pancreatic and colorectal cancer.

      OUTLINE:

      Patients are randomized to 1 of 4 arms.

      ARM I: Patients undergo surgery.

      ARM II: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60
      minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.

      ARM III: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and
      ipilimumab IV over 90 minutes on day 1. Patients then proceed to surgery 22-36 days after
      drug administration.

      ARM IV: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and
      nivolumab IV over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug
      administration.

      After completion of study treatment, patients are followed up at 90 days and then every 12
      weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (surgery)Active ComparatorPatients undergo surgery.
    Arm II (VX15/2503, surgery)ExperimentalPatients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    • Anti-SEMA4D Monoclonal Antibody VX15/2503
    Arm III (VX15/2503, ipilimumab, surgery)ExperimentalPatients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    • Anti-SEMA4D Monoclonal Antibody VX15/2503
    • Ipilimumab
    Arm IV (VX15/2503, nivolumab, surgery)ExperimentalPatients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    • Anti-SEMA4D Monoclonal Antibody VX15/2503
    • Nivolumab

    Eligibility Criteria

            Inclusion Criteria:
    
              -  For patients with pancreatic cancer:
    
                   -  Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma
    
                   -  Cancer confirmed to be surgically resectable, with surgery evaluation with
                      planned resection
    
                   -  Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant
                      chemoradiation
    
                   -  No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
    
              -  For patients with metastatic colorectal cancer:
    
                   -  Stage IV histologically-proven colorectal adenocarcinoma
    
                   -  Liver metastasis confirmed to be surgically resectable, with surgery evaluation
                      and planned resection; may have minimal extrahepatic disease that is determined
                      to be resectable
    
                   -  Tumor must be confirmed to be microsatellite stable (MSS); if not already
                      reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we
                      will be able to perform this at Emory University
    
                   -  No prior immunotherapy
    
                   -  No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    
              -  Absolute neutrophil count ≥ 1,500 cells/µL
    
              -  Platelets ≥ 100,000/µL
    
              -  Hemoglobin ≥ 9.0 g/dL (may receive packed red blood cell [prbc] transfusion)
    
              -  Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
    
              -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    
              -  Albumin ≥ 3.0 g/dL
    
              -  Serum creatinine ≤ 1.5 x ULN
    
              -  Calculated creatinine clearance of ≥ 50 mL/min
    
              -  International normalized ratio (INR) ≤ 1.5; anticoagulation is allowed only with low
                 molecular weight heparin (LMWH); patient receiving LMW heparin on stable therapeutic
                 dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial
    
              -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
                 tests, and other study procedures
    
              -  Ability to understand and willingness to sign a written informed consent document
    
              -  Female subjects of childbearing potential must agree to use adequate contraception
                 (e.g., hormonal or barrier method of birth control; abstinence) for the duration of
                 study treatment and 3 months after completion
    
              -  Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for
                 the duration of study treatment and 3 months after completion
    
              -  Female subjects of childbearing age must have a negative serum pregnancy test at study
                 entry
    
            Exclusion Criteria:
    
              -  Poor venous access for study drug administration
    
              -  Determined not to be a surgical candidate due to medical co-morbidities
    
              -  Treatment with chronic immunosuppressants (e.g., cyclosporine following
                 transplantation)
    
              -  Prior organ allograft or allogeneic bone marrow transplantation
    
              -  Subjects with any active autoimmune disease or history of known or suspected
                 autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy,
                 type I diabetes mellitus, residual hypothyroidism, psoriasis not requiring systemic
                 treatment, or conditions not expected to recur in the absence of an external trigger
                 are permitted to enroll
    
              -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
                 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
                 days of study drug administration; inhaled or topical steroids and adrenal replacement
                 doses > 10 mg daily prednisone equivalents are permitted in the absence of active
                 autoimmune disease
    
              -  Women who are pregnant or lactating
    
              -  Uncontrolled intercurrent illness including, but not limited to, human
                 immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
                 therapy, ongoing or active infection, symptomatic congestive heart failure (New York
                 Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular
                 arrhythmia, or psychiatric illness/social situations that would limit compliance with
                 study requirements
    
              -  Other medications, or severe acute/chronic medical or psychiatric condition, or
                 laboratory abnormality that may increase the risk associated with study participation
                 or study drug administration, or may interfere with the interpretation of study
                 results, and in the judgment of the investigator would make the subject inappropriate
                 for entry into this study
    
              -  Clinical evidence of bleeding diathesis or coagulopathy
    
              -  Patients with prior malignancies, including pelvic cancer, are eligible if they have
                 been disease free for > 5 years; patients with prior in situ carcinomas are eligible
                 provided there was complete removal
    
              -  Active bacterial or fungal infections requiring systemic treatment within 7 days of
                 treatment
    
              -  Use of other investigational drugs (drugs not marked for any indication) within 28
                 days or at least 5 half-lives (whichever is longer) before study drug administration
    
              -  History of severe hypersensitivity reactions to other monoclonal antibodies
    
              -  Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Evaluate treatment effects of the study drugs on tumor cluster of differentiation 8+ (CD8+) T cell infiltration between the treatment groups.
    Time Frame:Up to 4 years from date of last treatment dose
    Safety Issue:
    Description:CD8+ T cells in tumor samples will be identified by immunohistochemistry and immunofluorescence staining, and we will quantitate the percentage and staining of the cells in the pancreatic and liver tissue with Integrated Cellular Imaging.

    Secondary Outcome Measures

    Measure:Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events scale version 4.0
    Time Frame:Up to 4 years from the date of last treatment dose
    Safety Issue:
    Description:Summary statistics will be presented for all safety analyses. Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity. Adverse events will be classified using MedDRA System Organ Classes and Preferred Terms.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Emory University

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