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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 : Not yet recruiting
First Posted : April 2, 2019
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

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.

Condition or disease Intervention/treatment Phase
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 Drug: Aspirin Procedure: Radical Prostatectomy Biological: Recombinant Interferon Alfa-2b Drug: Rintatolimod Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : January 2, 2022
Estimated Study Completion Date : January 2, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Arm I (aspirin, interferon alpha, rintatolimod, surgery)
Patients receive aspirin PO TID 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.
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

Experimental: Arm II (aspirin, rintatolimod, surgery)
Patients receive aspirin PO TID 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.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Procedure: Radical Prostatectomy
Undergo radical prostatectomy
Other Name: 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 Name: Prostatovesiculectomy




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Number of patients with Surgical margin positivity [ Time Frame: Up to 3 years ]
  3. 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.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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]) =< 2.5 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 gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years. Patients with ulceration, bleeding or perforation in the lower bowel are not excluded.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899987


Locations
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United States, New York
Roswell Park Cancer Institute Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Gurkamal S. Chatta    716-845-3863    Gurkamal.Chatta@roswellpark.org   
Principal Investigator: Gurkamal S. Chatta         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Gurkamal S Chatta Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT03899987     History of Changes
Other Study ID Numbers: 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 )
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019

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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

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Genital Diseases, Male
Carcinoma
Aspirin
Interferons
Interferon alpha-2
Interferon-alpha
poly(I).poly(c12,U)
Poly I-C
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors