Radiotherapy and 6-month Androgen Deprivation Therapy With or Without Apalutamide in Intermediate and Limited High Risk Localized Prostate Cancer: a Phase III Study
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Disease-free survival
研究概览
简要总结
The main objective of the trial to determine if the combination of apalutamide with 6 months of androgen deprivation therapy by LHRH agonists in patients with intermediate and limited high-risk, localized prostate cancer receiving primary radiation therapy (RT) results in an improvement of disease-free survival (DFS) evaluated by the treating physician, in comparison to the combination of radiation and androgen deprivation therapy without the addition of apalutamide.
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 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of prostate adenocarcinoma diagnosed by ultrasound guided biopsy of the prostate containing 10-12 cores showing no neuroendocrine component
- •Either of: Favorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (3 +4) (ISUP Grade 2), or cT2b. Infavorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (4+3) (ISUP Grade 3), or cT2b. Limited high risk : PSA > 20 ng/mL or Gleason score >7 (ISUP Grade 4/5)
- •M0 by standard imaging work-up
- •Scheduled to be treated with primary prostate RT
- •WHO Performance Status ≤ 2
- •No risk of urinary retention based on the International Prostate Symptom Score (IPSS) : IPSS < 20
- •Adequate liver function determined by the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), < 2.5 x upper limit of normal (ULN). Total bilirubin <1.5 x upper limit of normal (ULN)
- •Adequate renal function: creatinine level < 2 x ULN
- •Serum albumin ≥ 3.0 g/dL
- •Serum potassium ≥ 3.5 mmol/L
- •Hemoglobin ≥ 10.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
- •Platelet count ≥ 100,000 x 109/L independent of transfusion and/or growth factors within 3 months prior to randomization
- •Be able to swallow whole study drug tablets
排除标准
- •cT2c, T3, T4 or pelvic lymph nodes involvement, as assessed by CT scan or MRI (cN1) or pelvic lymph node dissection (pN1)
- •Previous pelvic irradiation or radical prostatectomy.
- •Bilateral orchiectomy
- •Prior systemic (e.g., chemotherapy) or procedural (e.g., prostatectomy, cryotherapy) treatment for prostate cancer
- •Prior treatment with 5-alpha reductase inhibitors for benign prostatic hypertrophy not discontinued 4 weeks prior to randomization
- •Prior treatment with any LHRH agonist or antagonist, bicalutamide, flutamide or nilutamide, enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents for prostate cancer
- •Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy for prostate cancer
- •Other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has been cured for at least 5 years.
- •History of Ulcerative Colitis, Crohn's Disease, Ataxia Telangiectasia, systemic lupus erythematosus or Fanconi anemia
- •History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤ 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
- •Medications known to lower the seizure thresholdmust be discontinued or substituted at least 4 weeks prior to study entry
- •Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (e.g., heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval > 450 ms at baseline
- •Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
- •Bilateral hip prostheses
- •Prior treatment with systemic glucocorticoids ≤ 4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
- •Use of any investigational agent ≤ 4 weeks prior to randomization
- •Current chronic use of opioid analgesics for ≥3 weeks for oral or ≥ 7 days for non-oral formulations
- •Major surgery ≤ 4 weeks prior to randomization
- •Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or LHRHa agonists or any of the components of the formulations
- •Presence 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
研究组 & 干预措施
Arm A: ADT + radiation therapy
Patient will receive 2 injections of a three-monthly LHRH agonist depot plus non-steroidal anti-androgen (rescue treatment) (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Radiation Therapy (Other)
Arm A: ADT + radiation therapy
Patient will receive 2 injections of a three-monthly LHRH agonist depot plus non-steroidal anti-androgen (rescue treatment) (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Luteinising Hormone Releasing Hormone analog agonist (LHRHa) (Drug)
Arm A: ADT + radiation therapy
Patient will receive 2 injections of a three-monthly LHRH agonist depot plus non-steroidal anti-androgen (rescue treatment) (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Non-steroidal anti-androgen (Drug)
Arm B: ADT + radiation therapy + Apalutamide
Patients will receive 2 injections of a three-monthly LHRH agonist depot. Apalutamide treatment: 240 mg PO daily, started the same day as the first LHRHa injection, for 6 months.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Radiation Therapy (Other)
Arm B: ADT + radiation therapy + Apalutamide
Patients will receive 2 injections of a three-monthly LHRH agonist depot. Apalutamide treatment: 240 mg PO daily, started the same day as the first LHRHa injection, for 6 months.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Apalutamide (Drug)
Arm B: ADT + radiation therapy + Apalutamide
Patients will receive 2 injections of a three-monthly LHRH agonist depot. Apalutamide treatment: 240 mg PO daily, started the same day as the first LHRHa injection, for 6 months.
All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
干预措施: Luteinising Hormone Releasing Hormone analog agonist (LHRHa) (Drug)
结局指标
主要结局
Disease-free survival
时间窗: 7.8 years from First Patient In (FPI)
Events for this endpoint include loco-regional recurrence, distant metastases (radiologically or pathologically confirmed), death from any cause, whichever occurs first
次要结局
- Progression-free survival(7.8 years from First Patient In (FPI))
- Prostate-Specific Antigen (PSA) nadir(5.5 years from First Patient In (FPI))
- Distant Metastasis-free survival(7.8 years from First Patient In (FPI))
- Overall survival(7.8 years from First Patient In (FPI))
- Prostate cancer specific survival(7.8 years from First Patient In (FPI))
- Prostate-Specific Antigen (PSA) value(5.5 years from First Patient In (FPI))
- Adverse events graded according to the National Cancer Institute Common Occurrence of Adverse Events(7.8 years from First Patient In (FPI))
- Health-related quality of life(7.8 years from First Patient In (FPI))