A Phase II Randomized Open Label Study of Sipuleucel-T vs. Sipuleucel-T and Tasquinimod in Patients With Metastatic Castrate-Resistant Prostate Cancer (CRPC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Change in Immune Response Assessed by IFN-g ELISPOT Specific for PA2024
研究概览
简要总结
This randomized phase II trial studies how well sipuleucel-T with or without tasquinimod works in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Tasquinimod may stop the growth of prostate cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether sipuleucel-T is more effective with or without tasquinimod in treating prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether tasquinimod augments immune response to sipuleucel-T.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of the combination of sipuleucel-T and tasquinimod in patients with castration-resistant metastatic prostate cancer.
II. To obtain preliminary evidence of the clinical benefit of the combination of sipuleucel-T and tasquinimod; to include changes in prostate specific antigen (PSA) over time, and duration of progression-free survival/overall survival.
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
- •Metastatic asymptomatic or minimally symptomatic castration-resistant prostate cancer (CRPC) patients who are eligible for sipuleucel-T
- •Disease progression by PSA criteria (PSA Working Group Consensus Criteria Eligibility) and/or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Life expectancy >= 6 months
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Hemoglobin >= 100 g/L (>= 10 g/dL)
- •Leukocytes >= 3,000/mm^3
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Total bilirubin =< 1.5 x laboratory upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x laboratory upper limit of normal
- •Creatinine =< 1.5 x laboratory upper limit of normal or calculated creatinine clearance of >= 50 mL/min (please use institutional formula)
- •Prothrombin time (PT)/international normalized ratio (INR) =< 1.5
- •Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be < 1000 mg
- •Central nervous system (CNS): no recent history (within 6 month) of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases
- •Ability to understand and the willingness to sign a written informed consent document
- •Patient verbalizes the ability to swallow and retain oral medication
- •Subject 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
排除标准
- •Patients who have received systemic steroids within 4 weeks prior to starting study treatment
- •Patients who have received prior immunotherapies
- •History of therapy for an autoimmune disorder
- •Patients receiving any other investigational agents
- •Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Association class II, III, or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (less than the last 6 months), cardiac arrhythmia, history of cerebrovascular accident (CVA) within 6 months; no uncontrolled hypertension (defined as blood pressure of > 160/90 mmHg) on medication or, history of peripheral vascular disease
- •Ongoing treatment with warfarin unless the international normalized ratio (INR) is well controlled and below 4
- •History of psychiatric illness or social situations that would limit compliance with study requirements
- •History of pancreatitis
- •Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible
- •Systemic exposure to ketoconazole or other strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) isoenzyme inhibitors or inducers within 14 days prior to the start of study treatment; systemic exposure to aminodarone is not allowed within 1 year prior to the start of study treatment
- •Ongoing treatment with sensitive cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment
- •Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of therapy
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug
研究组 & 干预措施
Arm I (sipuleucel-T)
Patients receive sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (sipuleucel-T)
Patients receive sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Sipuleucel-T (Biological)
Arm II (tasquinimod, sipuleucel-T)
Patients receive tasquinimod PO QD beginning on day -14 and sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients continue on tasquinimod treatment after day 42 until disease progression.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (tasquinimod, sipuleucel-T)
Patients receive tasquinimod PO QD beginning on day -14 and sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients continue on tasquinimod treatment after day 42 until disease progression.
干预措施: Sipuleucel-T (Biological)
Arm II (tasquinimod, sipuleucel-T)
Patients receive tasquinimod PO QD beginning on day -14 and sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients continue on tasquinimod treatment after day 42 until disease progression.
干预措施: Tasquinimod (Drug)
结局指标
主要结局
Change in Immune Response Assessed by IFN-g ELISPOT Specific for PA2024
时间窗: Baseline up to 50 weeks
次要结局
- Duration of PSA Response(Up to 3 years)
- Change in PSA Response(Baseline to up to 3 years)
- Immune Response(Week 50)
- Immune Response (Arm 2 Only)(Week 0)
- Progression-free Survival(Up to 3 years)
- Time to PSA Progression(Up to 3 years)
- Objective Response Rates (Partial or Complete)(Up to 3 years)
- Frequency of Toxicities Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4(Up to 3 years)
- Overall Survival(Up to 3 years)