Clinical Trials /

Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery

NCT03899987

Description:

This phase II trial studies how well aspirin and rintatolimod with or without interferon-alpha 2b work in treating patients with prostate cancer before surgery. Aspirin may help to keep the prostate cancer from coming back. Rintatolimod may stimulate the immune system and interfere with the ability of tumor cells to grow and spread. Interferon-alpha 2b may improve the body's natural response to infections and may slow tumor growth. It is not yet known how well rintatolimod, aspirin, and interferon-alpha 2b work in treating patients with prostate cancer undergoing surgery.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery
  • Official Title: Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen

Clinical Trial IDs

  • ORG STUDY ID: I 77318
  • SECONDARY ID: NCI-2019-01192
  • SECONDARY ID: I 77318
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03899987

Conditions

  • Prostate Adenocarcinoma
  • Stage I Prostate Cancer AJCC v8
  • Stage II Prostate Cancer AJCC v8
  • Stage IIA Prostate Cancer AJCC v8
  • Stage IIB Prostate Cancer AJCC v8
  • Stage IIC Prostate Cancer AJCC v8
  • Stage III Prostate Cancer AJCC v8
  • Stage IIIA Prostate Cancer AJCC v8
  • Stage IIIB Prostate Cancer AJCC v8
  • Stage IIIC Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
AspirinAcetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, MeasurinArm I (aspirin, interferon alpha, rintatolimod, surgery)
Recombinant Interferon Alfa-2bAlfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Interferon Alfa-2B, Interferon Alpha-2b, Intron A, Sch 30500, Urifron, ViraferonArm I (aspirin, interferon alpha, rintatolimod, surgery)
RintatolimodAmpligen, AtvogenArm I (aspirin, interferon alpha, rintatolimod, surgery)

Purpose

This phase II trial studies how well aspirin and rintatolimod with or without interferon-alpha 2b work in treating patients with prostate cancer before surgery. Aspirin may help to keep the prostate cancer from coming back. Rintatolimod may stimulate the immune system and interfere with the ability of tumor cells to grow and spread. Interferon-alpha 2b may improve the body's natural response to infections and may slow tumor growth. It is not yet known how well rintatolimod, aspirin, and interferon-alpha 2b work in treating patients with prostate cancer undergoing surgery.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the immunomodulatory effectiveness of the combination of rintatolimod and aspirin
      with or without recombinant interferon alfa-2b (interferon [IFN]-alpha), in participants with
      localized prostate cancer undergoing radical prostatectomy.

      SECONDARY OBJECTIVES:

      I. Assess the safety and toxicity of the treatment combinations in participants with
      localized prostate cancer undergoing radical prostatectomy.

      II. Assess the antitumor activity between treatment arms.

      EXPLORATORY OBJECTIVES:

      I. Compare the resected tumor tissue specimen and surrounding tissue samples of both study
      arms (pre versus [vs] post-chemokine modulatory [CKM] treatment, with vs without CKM, CKM
      doublet vs CKM triplet) with regards to infiltrating T cell subtypes, effector T cell
      (Teff)/regulatory T cell (Treg) ratios, CD11b+ myeloid-derived suppressor cell (MDSC); the
      expression of chemokine receptors and immune checkpoint molecules on immune cells; local
      expression of Teff-attracting chemokines and Treg/MDSC-favoring chemokines; ribonucleic acid
      (RNA) signatures of groups of immune-regulatory genes that are modulated by the CKM regimen.

      OUTLINE: Patients are randomized to 1 of 3 arms.

      ARM I: Patients receive aspirin orally (PO) three times a day (TID) from day -5 to 7 days
      prior to surgery. Patients also receive recombinant interferon alfa-2b intravenously (IV)
      over 20 minutes and rintatolimod IV over 2 hours on days 1-3, 8-10 and 15-17 in the absence
      of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy
      on or between day 22-26.

      ARM II: Patients receive aspirin PO TID from day -5 to 7 days prior to surgery and
      rintatolimod IV over 2 hours on days 1-3, 8-10 and 15-17 in the absence of disease
      progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or
      between day 22-26.

      ARM III: Patients undergo radical prostatectomy about 4 weeks after enrollment.

      After completion of study treatment, patients are followed up at 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (aspirin, interferon alpha, rintatolimod, surgery)ExperimentalPatients receive aspirin PO BID on days -5 to 7. Patients also receive recombinant interferon alfa-2b IV over 20 minutes and rintatolimod IV over 2 hours on days 1-3, 8-10 and 15-17 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 22-26.
  • Aspirin
  • Recombinant Interferon Alfa-2b
  • Rintatolimod
Arm II (aspirin, rintatolimod, surgery)ExperimentalPatients receive aspirin PO BID on days -5 to 7 and rintatolimod IV over 2 hours on days 1-3, 8-10 and 15-17 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 22-26.
  • Aspirin
  • Rintatolimod
Arm III (radical prostatectomy)Active ComparatorPatients undergo radical prostatectomy about 4 weeks after enrollment.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed, localized prostate adenocarcinoma patients who are planning
                 to have a radical prostatectomy.
    
              -  Diagnostic prostate biopsy must have been obtained within 6 months patients who had
                 biopsies at outside facilities may be eligible if tissue availability and adequacy can
                 be confirmed by pathology.
    
              -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    
              -  Platelet >= 75,000/uL.
    
              -  Hemoglobin >= 9 g/dL.
    
              -  Hematocrit >= 27%.
    
              -  Absolute neutrophil count (ANC) >= 1500/uL.
    
              -  Creatinine < institutional upper limit of normal (ULN) OR creatinine clearance >= 50
                 mL/min for patients with creatinine levels greater than ULN.
    
              -  Total bilirubin =< 1.5 X institutional ULN.
    
              -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
                 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X
                 institutional ULN.
    
              -  Serum amylase and lipase =< 1.5 X institutional ULN.
    
              -  Participant or legal representative must understand the investigational nature of this
                 study and sign an Independent Ethics Committee/Institutional Review Board approved
                 written informed consent form prior to receiving any study related procedure.
    
            Exclusion Criteria:
    
              -  Patients currently treated with systemic immunosuppressive agents, including steroids,
                 are ineligible until 3 weeks after removal from immunosuppressive treatment.
    
              -  Patients who received hormonal therapy, 5-alpha reductase inhibitors (such as
                 finasteride, dutasteride), chemotherapy, radiotherapy, major surgery, or biologic
                 therapy within 3 weeks of protocol treatment.
    
              -  Patients with active prostatitis.
    
              -  Patients with active autoimmune disease or history of transplantation.
    
              -  Patients with comorbid medical conditions that render them unfit for surgery.
    
              -  Metastatic disease based on preoperative imaging.
    
              -  Cardiac risk factors including:
    
                   -  Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial
                      infarction, or ischemia) within 3 months of signing consent
    
                   -  Patients with a New York Heart Association classification of III or IV.
    
              -  History of upper and lower gastrointestinal ulceration, upper gastrointestinal
                 bleeding, or perforation within the past 3 years.
    
              -  History of bleeding disorders, known lesions at risk for bleeding, or history of
                 recent clinically significant bleed or hemorrhage (<3months).
    
              -  Prior allergic reaction or hypersensitivity to aspirin, or other nonsteroidal
                 antiinflammatory drugs (NSAIDs).
    
              -  Patients are ineligible if they plan on use of other NSAIDs at any dose during the
                 trial. Patients who agree to stop regular NSAIDs are eligible and no wash out period
                 is required.
    
              -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, or psychiatric illness/social situations that would limit compliance with
                 study requirements.
    
              -  Unwilling or unable to follow protocol requirements.
    
              -  Any condition which in the investigator?s opinion deems the participant an unsuitable
                 candidate to receive study drug.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Count of tumor infiltrating CD8+ lymphocytes
    Time Frame:Up to 3 years
    Safety Issue:
    Description:This will be assessed by the increase in the total number of tumor infiltrating CD8+ T cells in the radical prostatectomy specimen (measured as cell density of CD8+ cell by immunohistochemistry), comparing Arm A versus Arm B versus Arm C. Will be natural log transformed prior to analysis. The primary analysis will consist of testing the single degree of freedom planned contrast at alpha = .10 that the 3 treatment means are in the ratio of 3:2:1 (contrast coefficients 3, -2, -1) for groups A, B and C, respectively groups. If this test rejects the null hypothesis of no group differences, will proceed to estimate group means and pairwise differences between groups with 90% confidence intervals. Non-overlapping confidence intervals will serve as evidence of differential treatment effects.

    Secondary Outcome Measures

    Measure:Pathologic response
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and prostate specific antigen (PSA) response.
    Measure:Number of patients with Surgical margin positivity
    Time Frame:Up to 3 years
    Safety Issue:
    Description:
    Measure:PSA response
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and PSA response.
    Measure:Incidence of treatment-related adverse events
    Time Frame:Up to 30 days post treatment
    Safety Issue:
    Description:Will be evaluated with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Roswell Park Cancer Institute

    Last Updated

    December 4, 2019