APPROACH : Multimodal Approach in Patients With mHSPC. A Pragmatic Randomized Trial of Apalutamide Plus Androgen Deprivation Therapy (APA-ADT) Versus APA-ADT Plus Local Treatment. A Meet-URO 29 Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 566
- 试验地点
- 3
- 主要终点
- Radiographic Progression-Free Survival (rPFS)
研究概览
简要总结
Italian multicenter study, will enroll ~566 pts with oligometastatic hormone sensitive prostate cancer who are candidates to receive treatment with apalutamide.
After 6 months from the start of treatment, patients will be randomized to receive local treatment based on the investigator's choice ( either one between primary radiotherapy or cytoreductive prostatectomy), in addition to apalutamide, or to continue just with medical therapy.
详细描述
Primary end point: To determine whether treatment with apalutamide in combination with androgen-deprivative therapy for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy has better efficacy than medical treatment with apalutamide + ADT alone in terms of radiographic progression-free survival (rPFS), specifically time to radiographic progression in soft tissue per RECIST 1.1 or in bone per PCWG3 criteria by investigator, or death. Secondary end points: To evaluate tumor shrinkage after locoregional approach and to evaluate short and long term side effects after locoregional surgery or RT, time to PSA progression, time to castration resistance, cancer specific survival, overall survival and quality of life according to EPIC-26 and EQ-5D-5L questionnaires.
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
- •Age > 18
- •Histologically confirmed diagnosis of prostate adenocarcinoma
- •Metastatic disease documented by ≥1 bone lesion with Technetium 99m (99mTc) bone scan. Individuals with only one bone lesion should have confirmation of that lesion on CT or MRI.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) Grade ≤ 2
- •No previous treatment with antiandrogens or GnRH analogues, or a treatment ≤ 3 months.
- •No previous systemic or local treatment for prostate adenocarcinoma, including pelvic radiotherapy.
- •Laboratory values at the time of screening:
- •a. Neutrophils ≥ 1500/μL b. Hemoglobin ≥ 9.0 mg/μL (no transfusions in the past 28 days) c. Platelets ≥ 100,000/μL d. Creatinine ≤ 2 x upper limit of normal and serum albumin ≥ 3.0 g/dL f. Total bilirubin ≤ 1.5 x upper limit of normal [NOTE: In subjects with Gilbert syndrome, if total bilirubin is >1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤ 1.5 x ULN subjects may be eligible]; g. AST and ALT ≤ 2.5 x upper limit of normal
- •Able to swallow Apalutamide tablets whole.
- •All subjects must sign an Informed Consent Form indicating that they understand the purpose of the study and its procedures and intend to participate. The subject must be willing and must be able to comply with the restrictions specified in this protocol.
- •Inclusion criteria for cytoreductive surgery:
- •Age >18 years
- •Clinical stage cT3
- •Robot-assisted radical prostatectomy with iliac obturator lymphadenectomy
- •Surgical piece management criteria similar to Proteus criteria.
排除标准
- •Pathologic findings consistent with small cell, ductal, or neuroendocrine prostate cancer.
- •Known brain metastases.
- •Lymph node metastases only.
- •Visceral metastases.
- •Patients not eligible for surgery or radiotherapy.
- •Unacceptable increase in cardiovascular risk, defined as the occurrence of at least one of the following episodes in the 6 months prior to randomization: unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant thromboembolic events (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias .
- •Uncontrolled high blood pressure (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg).
- •Previous treatment with antiandrogens, GnRH analogues, or other systemic treatments for adenocarcinoma of the prostate.
- •Previous local treatment with surgery and/or radiotherapy.
- •Any prior malignancy (except adequately treated basal cell carcinoma or a squamous cell skin carcinoma, superficial bladder carcinoma, or any other in situ carcinoma currently in complete remission) within 5 years of randomization.
- •Known allergies, hypersensitivity or intolerance to the excipients of Apalutamide.
- •Patients who, within 28 days prior to randomisation, have received:
- •transfusions (red blood cells and/or platelets);
- •hematopoietic growth factors;
- •major surgery.
- •Symptomatic and/or chronic viral hepatitis; chronic liver disease; moderate or severe liver failure (class B and C according to the Child-Pugh scale); encephalopathy, ascites or thrombo-haemorrhagic disorders secondary to liver failure.
- •Gastrointestinal disorders affecting drug absorption
- •Active infections requiring systemic therapy such as human immunodeficiency virus (HIV);
- •Any condition or situation which, in the judgment of the investigator, precludes participation in this trial.
- •Exclusion criteria for cytoreductive surgery:
- •Contraindication for surgery
研究组 & 干预措施
APA + ADT + RP/RT
Apalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT) plus clinician-driven choice local treatment with Radiotherapy or Radical Prostatectomy, six months after starting treatment with apalutamide
干预措施: APA + ADT (Drug)
APA + ADT + RP/RT
Apalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT) plus clinician-driven choice local treatment with Radiotherapy or Radical Prostatectomy, six months after starting treatment with apalutamide
干预措施: Local Treatmetn RT or RP (Procedure)
APA + ADT
Apalutamide 240 mg, four 60 mg tablets as an oral single daily dose, according to clinical practice, plus Androgen Deprivation Therapy (ADT)
干预措施: APA + ADT (Drug)
结局指标
主要结局
Radiographic Progression-Free Survival (rPFS)
时间窗: Up to 48 months
Evaluation of the efficacy of treatment with APA+ADT for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy compared to treatment with APA+ ADT alone in terms of Radiographic Progression-Free Survival (rPFS) in patients with hormone prostate adenocarcinoma -susceptible with low-volume metastatic disease.
次要结局
- Local event - free survival(Up to 48 months)
- Local treatment - free survival(Up to 48 months)