A Randomized, Open-label, Phase 2 Study of Sipuleucel-T With Concurrent Versus Sequential Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 19
- 主要终点
- To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI).
研究概览
简要总结
This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide.
详细描述
This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide. This study consists of 3 phases. The screening phase will begin at the completion of the informed consent process and continue through registration. The active phase will begin at registration and continue through the post-treatment visit (30 to 37 days following the last study treatment). The long term follow-up (LTFU) phase will begin after the post-treatment visit and will continue until the subject's death or until Dendreon terminates the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Written informed consent provided prior to the initiation of study procedures.
- •Age ≥ 18 years.
- •Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen.
- •Metastatic disease as evidenced by bone metastasis or lymph node metastasis.
- •Castrate-resistant prostate cancer as demonstrated by one of the following:
- •Prostate specific antigen progression.
- •Progression of measurable disease.
- •Progression of non-measurable disease by soft tissue disease or bone disease.
- •Castration levels of testosterone (≤ 50 ng/dL) achieved via medical or surgical castration.
- •Serum PSA (Prostate specific antigen) ≥ 2.0 ng/mL.
- •Screening ECOG (The Eastern Cooperative Oncology Group )performance status ≤ 1
- •Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results obtained ≤ 28 days prior to registration.
- •Negative serology test for human immunodeficiency virus 1 and
- •Resides within driving distance (round trip within 1 day) of the clinical trial site for the duration of the active phase.
排除标准
- •The presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites.
- •Spinal cord compression, imminent long bone fracture, or any other condition that is likely to require radiation therapy and/or steroids for pain control during the active phase.
- •History of stage 3 or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease free at the time of registration. Subjects with a history of stage 1 or 2 cancer must have been adequately treated and been disease free for ≥ 3 years at the time of registration.
- •History of seizures or of predisposing factors for seizures.
- •Child-Pugh Class C hepatic insufficiency.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T, GM-CSF or granulocyte colony stimulating factor (G-CSF).
- •Previous treatment with sipuleucel-T or enrollment in a sipuleucel-T trial, regardless of whether the subject received sipuleucel-T or control.
- •Previous treatment with enzalutamide.
- •Previous treatment with abiraterone acetate.
- •Previous treatment with ipilimumab.
- •Previous treatment with ketoconazole other than topical use or for treatment of infections (e.g., oral thrush); most recent use must have been ≥ 7 days prior to registration.
- •Previous treatment with any immunotherapy or investigational vaccine.
- •A requirement for ongoing systemic immunosuppressive therapy. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed.
- •Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason ≤ 2 years prior to registration.
- •Use of concomitant medications that may lower the seizure threshold or the use of antiseizure medications ≤ 1 year prior to registration.
- •Received GM-CSF or G-CSF ≤ 90 days prior to registration.
- •Ongoing non-steroidal antiandrogen withdrawal response.
- •Any of the following medications or interventions ≤ 28 days prior to registration:
- •Radiation therapy, either via external beam or brachytherapy.
- •Any systemic steroid. Use of inhaled, intra-nasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed.
- •Any systemic therapy for prostate cancer, except for ADT (Androgen deprivation therapy).
- •Any investigational product for prostate cancer.
- •Major surgery requiring general anesthesia, with the exception of placement of central venous catheters.
- •Inducers and inhibitors of cytochrome P450 (CYP) enzyme CYP2C8 (gemfibrozil and rifampin).
- •Medications that are metabolized by CYP3A4, CYP2C9, or CYP2C19 that have a narrow therapeutic index.
- •Inducers of CYP3A4 (including but not limited to phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital).
- •A requirement for treatment with opioid analgesics for cancer-related pain ≤ 21 days prior to registration.
- •An active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5˚ F or 38.1˚ C) ≤ 1 week prior to registration.
- •Any medical intervention, any other condition, or any other circumstance which could compromise adherence with study requirements or otherwise compromise the study's objectives.
研究组 & 干预措施
Concurrent Arm
Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.
干预措施: sipuleucel-T (Biological)
Concurrent Arm
Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.
干预措施: enzalutamide (Drug)
Sequential Arm
Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.
干预措施: sipuleucel-T (Biological)
Sequential Arm
Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.
干预措施: enzalutamide (Drug)
结局指标
主要结局
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI).
时间窗: Each patient was followed for up to 52 weeks after the first dose of sipuleucel-T. Immune sample draws during the treatment period (Week 0 through Week 4) were to be performed at the patient's pre-leukapheresis visits (Pre-Leuk 2 and Pre-Leuk 3).
PA2024-specific T cell proliferation responses over time will be compared between the concurrent arm and sequential arm using a repeated measurement mixed model analysis. The unit of analysis for the T cell proliferation data is the stimulation index, defined as the median 3H uptake of 3 wells exposed to antigen divided by the median 3H thymidine uptake of 3 wells exposed to media. The stimulation index will be log-transformed prior to analysis.
次要结局
未报告次要终点