Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Count of tumor infiltrating CD8+ lymphocytes
研究概览
简要总结
This phase II trial studies how well enteric-coated (EC) aspirin and rintatolimod with or without interferon-alpha 2b work in treating patients with prostate cancer before surgery. EC 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, EC aspirin, and interferon-alpha 2b work in treating patients with prostate cancer undergoing surgery.
详细描述
PRIMARY OBJECTIVES:
I. Assess the immunomodulatory effectiveness of the combination of rintatolimod and EC 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Arm I (EC 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..
干预措施: Rintatolimod (Drug)
Arm I (EC 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..
干预措施: EC Aspirin (Drug)
Arm I (EC 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..
干预措施: Radical Prostatectomy (Procedure)
Arm II (EC 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.
干预措施: EC Aspirin (Drug)
Arm II (EC 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.
干预措施: Radical Prostatectomy (Procedure)
Arm III (radical prostatectomy)
Patients undergo radical prostatectomy about 4 weeks after enrollment.
干预措施: Radical Prostatectomy (Procedure)
Arm II (EC 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.
干预措施: Rintatolimod (Drug)
Arm I (EC 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..
干预措施: Recombinant Interferon Alfa-2b (Biological)
结局指标
主要结局
Count of tumor infiltrating CD8+ lymphocytes
时间窗: 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.
次要结局
- Pathologic response(Up to 3 years)
- Number of patients with Surgical margin positivity(Up to 3 years)
- PSA response(Up to 3 years)
- Incidence of treatment-related adverse events(Up to 30 days post treatment)