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

Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen

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.

Study Overview

• Status: Suspended
• Conditions: Prostate Adenocarcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8
• Intervention / Treatment: Drug: Aspirin; Procedure: Radical Prostatectomy; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

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) two times a day (BID) from day -7 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, and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.

ARM II: Patients receive aspirin PO BID from day -7 to 7 days prior to surgery and rintatolimod IV over 2 hours on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.

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: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Negative hepatitis panel for patients with a history of Hepatitis
• Participant 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (aspirin, interferon alpha, rintatolimod, surgery); Patients receive aspirin PO BID on days -7 to 7. Patients also receive recombinant interferon alfa-2b IV over 20 minutes and rintatolimod IV over 2 hours on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24..	Drug: Aspirin; Given PO; Other Names: Acetylsalicylic Acid; ASA; Aspergum; Ecotrin; Empirin; Entericin; Extren; Measurin; Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: 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
Experimental: Arm II (aspirin, rintatolimod, surgery); Patients receive aspirin PO BID on days -7 to 7 and rintatolimod IV over 2 hours on days 1-3,and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.	Drug: Aspirin; Given PO; Other Names: Acetylsalicylic Acid; ASA; Aspergum; Ecotrin; Empirin; Entericin; Extren; Measurin; Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: Prostatovesiculectomy; Drug: Rintatolimod; Given IV; Other Names: Ampligen; Atvogen
Active Comparator: Arm III (radical prostatectomy); Patients undergo radical prostatectomy about 4 weeks after enrollment.	Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: Prostatovesiculectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of tumor infiltrating CD8+ lymphocytes	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.	Up to 3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: AIM ImmunoTech Inc.
• Investigators: Principal Investigator: Gurkamal S Chatta, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2019
• Primary Completion (Estimated): May 29, 2024
• Study Completion (Estimated): May 29, 2024

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 2, 2019

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Immunologic Factors; Aspirin; Interferons; Interferon-alpha; Interferon alpha-2; poly(I).poly(c12,U)
• Other Study ID Numbers: I 77318 (Other Identifier: Roswell Park Cancer Institute); NCI-2019-01192 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• 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