ENZA-p: A Randomised Phase II Trial Using PSMA as a Therapeutic Agent and Prognostic Indicator in Men With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide (ANZUP 1901)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 162
- 试验地点
- 30
- 主要终点
- Prostate Specific Antigen (PSA) Progression-Free Survival
研究概览
简要总结
This phase 2 randomised clinical trial will investigate the activity and safety of adding Lu-PSMA to enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC) not previously treated with chemotherapy.
详细描述
This is an open label, randomised, stratified, 2-arm, multicentre phase 2 clinical trial recruiting 160 participants over 12 months and followed until 150 events occurred (approximately another 18 months). Participants will be randomised to enzalutamide or enzalutamide and Lu-PSMA in a 1:1 ratio. A minimisation approach will be used to minimise chance imbalances across the following stratification factors: study site, volume of disease (>20 versus ≤20 sites of disease measured on 68Ga-PSMA PET/CT), prior treatment with early docetaxel for castration- sensitive disease (yes vs no), and prior treatment with early abiraterone for castration-sensitive disease (yes vs no).
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
- •Males aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
- •Documented histopathology of prostate adenocarcinoma (no features of neuroendocrine carcinoma) OR
- •Metastatic disease typical of prostate cancer
- •Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
- •Progressive disease with rising PSA defined by PCWG3 criteria (sequence of 2 rising values at a minimum of 1-week intervals) AND PSA ≥ 5 ng/mL.
- •At least 2 of the following risk factors for early treatment failure with enzalutamide:
- •LDH ≥ ULN
- •ALP ≥ ULN
- •Albumin <35 g/L
- •De novo metastatic disease (M1) at initial diagnosis *
- •<3 years since initial diagnosis
- •>5 bone metastases *
- •Visceral metastases *
- •PSA doubling time <84 days
- •Pain requiring opiates for >14 days
- •Prior treatment with abiraterone * Based on conventional imaging (CT and/or bone scan)
- •Target or non-target lesions according to RECIST 1.1
- •Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as SUVmax >15 at a single site (regardless of lesion size) and SUV max >10 at sites of disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
- •ECOG performance status 0-2
- •Adequate renal function:
- •- Creatinine clearance ≥ 40mL/ min
- •Adequate liver function:
- •Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin)
- •AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
- •Adequate bone marrow function:
- •Platelets ≥ 100 x109/L
- •Haemoglobin ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
- •Neutrophils > 1.5 x109/L
- •Estimated life expectancy > 12 weeks
- •Study treatment both planned and able to start within 21 days of randomisation
- •Willing and able to comply with all study requirements (including both treatments: enzalutamide and Lu-PSMA), and all required study assessments
- •Signed, written, informed consent
排除标准
- •Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate
- •68Ga-PSMA PET/CT SUVmax < 10 at a site of measurable disease > 10mm
- •Prior treatment with enzalutamide, darolutamide, or apalutamide. Prior treatment with abiraterone is allowed.
- •Prior treatment with any PSMA-targeted radiotherapy
- •Prior chemotherapy for mCRPC. Prior docetaxel in castration-sensitive setting is permitted
- •History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours)
- •Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
- •Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
- •Men in sexual relationships with women of reproductive potential who are not willing/able to use medically acceptable forms of barrier contraception
- •History of:
- •seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
- •loss of consciousness or transient ischemic attack within 12 months of randomization
- •significant cardiovascular disease within the last 3 months: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater, see Appendix 4), ongoing arrhythmias of Grade > 2, thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
研究组 & 干预措施
Lu-PSMA + Enzalutamide
Lu-PSMA - 7.5 GBq (± 10%): doses 1 and 2 (Days 15 and 57). Doses 3 and 4 (Days 113 and 169) will be given following result of PSMA PET/CT scans at Day 92.
Enzalumatide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.
干预措施: Lu-PSMA (Drug)
Lu-PSMA + Enzalutamide
Lu-PSMA - 7.5 GBq (± 10%): doses 1 and 2 (Days 15 and 57). Doses 3 and 4 (Days 113 and 169) will be given following result of PSMA PET/CT scans at Day 92.
Enzalumatide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.
干预措施: Enzalutamide (Drug)
Enzalutamide
Enzalutamide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Prostate Specific Antigen (PSA) Progression-Free Survival
时间窗: Date of randomisation to the date of first evidence of PSA progression - assessed up to study completion, approximately 4 years from recruitment.
PSA progression is defined as a rise in PSA by more than or equal to 25% AND more than or equal to 2 ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later.
次要结局
- Radiographic Progression-Free Survival(Date of randomisation to the date of first evidence of radiographic progression on imaging. Assessed every 12 weeks through study completion, approximately 4 years from start of recruitment.)
- Pain response and Progression-Free Survival(Date of randomisation through study completion, approximately 4 years from start of recruitment)
- Clinical Progression-Free Survival(Date of randomisation to the date of first clinical evidence of disease progression or death from any cause. Assessed up to study completion approximately 4 years from recruitment.)
- Frequency and Severity of Adverse Events(Through study completion, approximately 4 years from recruitment.)
- Prostate Specific Antigen (PSA) response rate(Date of randomisation through study completion, approximately 4 years from start of recruitment. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA response)
- Aspects of Health-related Quality of life (HRQL)(Assessed every 4-6 weeks, through study completion, approximately 4 years from recruitment.)