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

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ClinicalTrials.gov Identifier: NCT03899987
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : July 8, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
AIM ImmunoTech Inc.
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE March 15, 2019
First Posted Date  ICMJE April 2, 2019
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE November 29, 2019
Estimated Primary Completion Date January 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
Count of tumor infiltrating CD8+ lymphocytes [ Time Frame: Up to 3 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
  • Pathologic response [ Time Frame: Up to 3 years ]
    Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and prostate specific antigen (PSA) response.
  • Number of patients with Surgical margin positivity [ Time Frame: Up to 3 years ]
  • PSA response [ Time Frame: Up to 3 years ]
    Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and PSA response.
  • Incidence of treatment-related adverse events [ Time Frame: Up to 30 days post treatment ]
    Will be evaluated with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Pathologic response [ Time Frame: Up to 3 years ]
    Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and prostate specific antigen (PSA) response.
  • Surgical margin positivity [ Time Frame: Up to 3 years ]
  • PSA response [ Time Frame: Up to 3 years ]
    Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and PSA response.
  • Incidence of treatment-related adverse events [ Time Frame: Up to 30 days post treatment ]
    Will be evaluated with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery
Official Title  ICMJE Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Aspirin
    Given PO
    Other Names:
    • Acetylsalicylic Acid
    • ASA
    • Aspergum
    • Ecotrin
    • Empirin
    • Entericin
    • Extren
    • Measurin
  • Procedure: Radical Prostatectomy
    Undergo radical prostatectomy
    Other Name: Prostatovesiculectomy
  • Biological: Recombinant Interferon Alfa-2b
    Given IV
    Other Names:
    • Alfatronol
    • Glucoferon
    • Heberon Alfa
    • IFN alpha-2B
    • Interferon alfa 2b
    • Interferon Alfa-2B
    • Interferon Alpha-2b
    • Intron A
    • Sch 30500
    • Urifron
    • Viraferon
  • Drug: Rintatolimod
    Given IV
    Other Names:
    • Ampligen
    • Atvogen
Study Arms  ICMJE
  • Experimental: Arm I (aspirin, interferon alpha, rintatolimod, surgery)
    Patients 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.
    Interventions:
    • Drug: Aspirin
    • Procedure: Radical Prostatectomy
    • Biological: Recombinant Interferon Alfa-2b
    • Drug: Rintatolimod
  • Experimental: Arm II (aspirin, rintatolimod, surgery)
    Patients 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.
    Interventions:
    • Drug: Aspirin
    • Procedure: Radical Prostatectomy
    • Drug: Rintatolimod
  • Active Comparator: Arm III (radical prostatectomy)
    Patients undergo radical prostatectomy about 4 weeks after enrollment.
    Intervention: Procedure: Radical Prostatectomy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 4, 2019)
45
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2019)
60
Estimated Study Completion Date  ICMJE January 2, 2023
Estimated Primary Completion Date January 2, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03899987
Other Study ID Numbers  ICMJE I 77318
NCI-2019-01192 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 77318 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • AIM ImmunoTech Inc.
Investigators  ICMJE
Principal Investigator: Gurkamal S Chatta Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP