An Exploratory Phase 2, Open-label, Single-arm, Efficacy and Imaging Study of Oral Enzalutamide (XTANDI) Androgen Receptor (AR)-Directed Therapy in Hormono-Sensitive Patients With Metastatic Prostate Cancer (Hormono-sensitive Patients)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) at 6 and 12 months.
研究概览
简要总结
The aim of the study is to assess the clinical utility of 11C or 18F-Choline Positron Emission Tomography (PET)/Computed Tomography (CT) scan, Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in Hormono-Sensitive Metastatic Prostate Cancer patients.
The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide.
In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.
详细描述
Metastatic prostate cancer patients eligible for 1st line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs. All subjects will undergo Choline (11C or 18F)-PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor (AR)-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Male aged 18 years or older;
- •Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
- •Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 2 ng/mL but preferably >20 ng/mL;
- •Progressive disease defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 11C or 18F-Choline PET/CT, Whole Body MRI or both;
- •No prior treatment with cytotoxic chemotherapy;
- •Eastern Cooperative Oncology Group (ECOG) score 0-2;
- •A life expectancy of at least 12 months;
- •Written informed consent;
排除标准
- •Treatment with androgen deprivation therapy with a gonadotropin-releasing hormone analogue, luteinizing hormone-releasing hormone antagonist, or bilateral orchiectomy within 6 months of enrolment (Day1 visit);
- •Treatment with anti-androgens such as bicalutamide, nilutamide or flutamide within 6 weeks of enrolment (Day 1 visit);
- •Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens, cyproterone acetate within 4 weeks of enrolment (Day 1 visit);
- •Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
- •Known or suspected brain metastasis or active leptomeningeal disease;
- •History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer;
- •Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
- •Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
- •Hemoglobin <6 mmol/L, White blood cells < 4.0 x 10^9/L, Platelets < 100 x 10^9/L;
- •History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit);
- •Contra-indication for MRI (e.g. pacemaker).
研究组 & 干预措施
Single arm
Experimental: Single arm Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment.
干预措施: Enzalutamide (Drug)
Single arm
Experimental: Single arm Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment.
干预措施: 11C or 18F-Choline PET/CT (Procedure)
Single arm
Experimental: Single arm Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment.
干预措施: Whole body MRI (Procedure)
Single arm
Experimental: Single arm Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment.
干预措施: Bone scan (Procedure)
结局指标
主要结局
Progression-Free Survival (PFS) at 6 and 12 months.
时间窗: 6 and 12 months
Radiological progression is defined by any of the following criteria: * Soft tissue lesions: Progressive disease on Choline (11C or 18F) PET/CT or Whole Body MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions. * Conversion of the Choline (11C or 18F) PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 6 and 12 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
次要结局
- Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression(6 and 12 months)
- Biochemical response defined as prostate-specific antigen (PSA) nadir(12 months)
- PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements)(12 months)
- Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria(6 and 12 months)
- Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments(12 months)
- Circulating tumour cell (CTC) measurements and comparison with radiological PFS at 6 and 12 months(6 and 12 months)
- Percent change from baseline in serum concentration of circulating testosterone (T)(12 months)
- Percent change from baseline in serum concentration of dihydrotestosterone (DHT)(12 months)
- Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG)(12 months)
- Percent change from baseline in serum concentration of androstenedione (A)(12 months)
- Number of participants with changes in biomarkers of bone turnover correlated to PSA(12 months)
- Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation(6 and 12 months)
- Time to symptomatic progression (including death due to prostate cancer)(12 months)
- Time to first radiological or symptomatic progression(6 and 12 months)
- Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation(12 months)
- Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire(6 and 12 months)
- Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D)(6 and 12 months)
- Changes in Sexual Function (IIEF)(6 and 12 months)
- Changes in Karnofsky score(6 and 12 months)
- Changes in visual analogue scale (VAS) for tumour-related pain(6 and 12 months)
- Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan(6 and 12 months)