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临床试验/NCT03080116
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

Universitaire Ziekenhuizen KU Leuven1 个研究点 分布在 1 个国家目标入组 90 人开始时间: 2019年3月28日最近更新:
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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)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

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

申办方类型
Other
责任方
Sponsor

研究点 (1)

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