NCT03080116进行中（未招募）2 期
Neoadjuvant Degarelix +/- Apalutamide (ARN-509) Followed by Radical Prostatectomy for Intermediate and High-risk Prostate Cancer: a Randomized, Placebo-controlled Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Minimal Residual Disease (MRD)
研究概览
简要总结
RATIONALE: Neoadjuvant hormonal therapy using luteinizing hormone releasing hormone (LHRH) agonists and/or anti-androgens has already demonstrated to downstage primary prostate cancer in patients treated by radical prostatectomy without a survival benefit. There is no evidence yet of a survival impact of LHRH antagonist (LHRHa) +/- new-generation anti-androgens in this setting. Thus novel studies are needed to assess this treatment combination.
PURPOSE: To assess the difference in treatment antitumor effect between arms by measuring pathological tumor volume with minimal residual disease (MRD) following radical prostatectomy + pelvic lymph-node dissection (RP + PLND) for intermediate or high-risk prostate cancer patients.
详细描述
PRIMARY OBJECTIVE: To assess the difference in antitumor effect between the treatment arms by measuring MRD following radical prostatectomy.
SECONDARY OBJECTIVES: To measure differences between study arms in
- Proportions of post neoadjuvant prostate specific antigen (PSA) ≤ 0.3 ng/ml as a predictor of prostate cancer mortality
- T down-staging, complete pathological response, PSA kinetics, Testosterone kinetics, operation time, blood loss, grade of surgical difficulty
- New generation hybrid imaging 68Ga PSMA (Prostate-Specific Membrane Antigen) PET/MR (Positron emission tomography/Magnetic Resonance) derived parameters
- Early biochemical recurrence as prognostic factor of prostate cancer mortality
- Transcriptome and genome
- Tissue microarrays (TMA) protein expression (DNA repair, resistance etc.) by immunohistochemistry
- Perioperative safety and tolerability
- Quality of life, erection recovery, continence through validated preoperative and postoperative questionnaires pre and postop (IEEF5, ICIQ, EORTC QLQ-C30)
OUTLINE: interventional, single center, phase II, randomized, double blind, placebo controlled trial.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- •Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
- •Male aged 18 years or older (within 80 years)
- •Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- •Diagnosis of intermediate (at least 2 of the following factors: cT2b, biopsy GS 7, PSA 10-20ng/ml) or high-risk prostatic adenocarcinoma (clinical stage≥T2c and/or biopsy GS≥8 and/or PSA>20ng/ml), cN0-cN1, cM
- •Patient amenable for open or robotic radical prostatectomy + pelvic lymph node dissection
- •ECOG performance status: 0-1
- •Adequate organ function as defined by the following criteria:
- •White blood cells (WBC) ≥ 4.0 x109/L
- •Platelet count ≥ 100 x109/L
- •Hemoglobin ≥9 g/dl
- •Creatinine ≤ 2 x ULN
- •Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x upper limit of normality (ULN)
- •Total serum bilirubin ≤1.5 x ULN.
排除标准
- •Previous surgical/endoscopic treatments for prostatic disease
- •Herbal and non-herbal products that in the opinion of the investigator may decrease PSA levels
- •cM1 disease
- •Any contraindication for PET or MR investigations
- •History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
- •Medications known to lower the seizure threshold
- •History of:
- •Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer currently in complete remission) within 5 years prior to randomization
- •Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
- •Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥100 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
- •Gastrointestinal disorder affecting absorption
- •Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.
研究组 & 干预措施
ARN-509 + degarelix
Experimental
Treatment period of 12 weeks before RP + PLND.
干预措施: ARN-509 (Drug)
ARN-509 + degarelix
Experimental
Treatment period of 12 weeks before RP + PLND.
干预措施: Degarelix (Drug)
placebo + degarelix
Active Comparator
Treatment period of 12 weeks before RP + PLND.
干预措施: Degarelix (Drug)
placebo + degarelix
Active Comparator
Treatment period of 12 weeks before RP + PLND.
干预措施: Placebo (Other)
结局指标
主要结局
Minimal Residual Disease (MRD)
时间窗: After 12 weeks of neoadjuvant therapy + RP + PLND
Proportions of MRD between arms. MRD: tumor volume ≤ 0.25 cm3
次要结局
- Complete pathological response rates(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Difference in proportions of patients with pN1 disease.(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Standardized Uptake Value (SUV) on pelvic [68]Ga PSMA PET/MR per arm(At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND)
- Standardized Uptake Value (SUV) on pelvic [68]Ga PSMA PET/MR and tumour volume(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Difference in proportions of pathological downstage(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Genomic subtyping by exome-sequencing(At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND)
- Differences in proportions of surgical complications between arms(Up to 6 weeks post RP + PLND)
- Standardized Uptake Value (SUV) on pelvic [68]Ga PSMA PET/MR between arms(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](From patient inclusion until RP + PLND)
- Pathway profiling and Gene Set Enrichment Analyses(At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND)
- Survival(Up to 36 months)
- Proteins expression in prostatic tumour TMA's (tissue microarrays)(After 12 weeks of neoadjuvant therapy + RP + PLND)
- PSA kinetics(Up to 40 months)
- PSA nadir </=0.3ng/ml after neoadjuvant treatment(After 12 weeks of neoadjuvant therapy before RP + PLND)
- Quality of life(Up to 40 months)
- Erection state(Up to 40 months)
- Transcriptome analysis by microarray expression platform(At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND)
- Testosterone kinetics(Up to 40 months)
- Peri-operative features(up to (about) 5 hours)
- Continence(Up to 40 months)
- Magnetic resonance (MR) and tumor volume (TV) per arm(At baseline and after12 weeks of neoadjuvant therapy + RP + PLND)
- Magnetic resonance (MR) and tumor volume (TV) between arms(At baseline and after12 weeks of neoadjuvant therapy + RP + PLND)
- Standardized Uptake Value (SUV) on prostate [68]Ga PSMA PET/MR and Immunohistochemistry(After 12 weeks of neoadjuvant therapy + RP + PLND)
- PI-RADS score and Gleason score(After 12 weeks of neoadjuvant therapy + RP + PLND)
- PI-RADS between arms at MR(After 12 weeks of neoadjuvant therapy + RP + PLND)
- Down-staging at imaging(At baseline and after 12 weeks of neoadjuvant therapy + RP + PLND)
研究者
研究点 (1)
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