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

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

Tracking Information

• First Submitted Date: March 15, 2019
• First Posted Date: April 2, 2019
• Last Update Posted Date: July 8, 2020
• Actual Study Start Date: November 29, 2019
• Estimated Primary Completion Date: January 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 4, 2019): 45
• Original Estimated Enrollment (submitted: April 1, 2019): 60
• Estimated Study Completion Date: January 2, 2023
• Estimated Primary Completion Date: January 2, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03899987
• 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 )
• 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: Not Provided
• Responsible Party: Roswell Park Cancer Institute
• Study Sponsor: Roswell Park Cancer Institute

Collaborators

• National Cancer Institute (NCI)
• AIM ImmunoTech Inc.

Investigators

• Principal Investigator: Gurkamal S Chatta; Roswell Park Cancer Institute

• PRS Account: Roswell Park Cancer Institute
• Verification Date: July 2020