A Phase II Study Comparing Salvage Radiotherapy in Combination With 6 Months of Androgen-deprivation Therapy Versus Anti-androgen Therapy With Apalutamide in Patients With Biochemical Progression After Radical Prostatectomy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 202
- 试验地点
- 9
- 主要终点
- EPIC-26 sexual domain score
研究概览
简要总结
This is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist (arm A) versus anti-androgen therapy (AAT) with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm) or 6 28-day cycles of apalutamide 240mg daily (interventional arm). The study will include a screening phase, treatment phase, and a post-treatment phase. The primary objective of the trial is to compare sexual function between the 2 groups based on the Expanded Prostate cancer Index Composite (EPIC)-26 sexual domain scores at 9 months after start of hormonal treatment.
详细描述
After radical prostatectomy, around one third of patients will have biochemical progression. Salvage radiotherapy (SRT) is still potentially curative, but about 40-50% of patients will progress further. Recently, success rates of SRT were significantly improved through the use of concomitant anti-androgen (AAT) or androgen-deprivation (ADT) therapy. In RTOG 96-01, 2 years of bicalutamide 150 mg resulted in a 5% overall survival benefit at 12-years. In GETUG-AFU 16, 5-year progression-free survival was significantly improved when SRT was combined with 6 months of an LHRH agonist. Based on GETUG-AFU 16, most radiation oncologists now combine SRT with at least 6 months of ADT. However, ADT comes with several serious side-effects, both physical (cardiovascular, metabolic, musculoskeletal) and psychological (sexual, emotional and cognitive). It appears worthwile to look for alternatives in the form of AAT. In that respect, apalutamide, a potent competitive and purely antagonistic second-generation anti-androgen, is the ideal candidate.
This trial is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of ADT (arm A) versus AAT with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of ADT with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm A) or 6 28-day cycles of apalutamide 240mg daily (interventional arm B).
The study will include a screening phase, treatment phase, and a post-treatment phase.
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Screening phase: allows for assessment of subject eligibility up to 35 days prior to randomization.
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Treatment phase: includes the hormonal treatment for 6 months, to be started at the most 2 weeks after randomization and standard salvage radiotherapy. During the treatment phase, patients will have 3 study visits:
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treatment initiation visit: first injection of LHRH (ant)agonist (arm A) or cycle 1, day 1 (C1D1) of apalutamide (arm B).
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Concurrent with RT visit: if necessary (depending on product prescribed) injection of LHRH (ant)agonist (arm A) or cycle 4, day 1 (C4D1) of apalutamide (arm B).
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End of treatment visit: at the end of the 6 months of hormonal therapy.
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Post-treatment phase: will begin after a subject completes the treatment phase and the end of treatment visit and will continue until the primary endpoint is reached, i.e. the 9-months (3 months after end of treatment visit) EPIC-26 sexual domain score.
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
- •Male, > 18 years old.
- •Histologically confirmed adenocarcinoma of the prostate.
- •Previous radical prostatectomy (RP), pT2-3, pN0 or pNx.
- •PSA detectable with confirmed rise (at least 2 weeks apart) at least 8 weeks after RP.
- •Hormone-naive disease.
- •Patients amendable to take oral medication.
- •Patients must have clinical laboratory values at screening:
- •Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
- •Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization
- •Serum albumin ≥3.0 g/dL
- •Serum creatinine <2.0 × upper limit of normal (ULN)
- •Serum potassium ≥3.5 mmol/L
- •Serum total bilirubin 1.5 × ULN (note: in subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN
- •Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.
- •Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
- •Patients who have received the information sheet and signed the informed consent form.
- •Patients must be willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
排除标准
- •Patients with severe erectile dysfunction according to international index of erectile function (IIEF-5) questionnaire (score 1-7).
- •Allergies, hypersensitivity or known intolerance to the study drugs or excipients.
- •History of any of the following:
- •Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
- •Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization.
- •Current evidence of any of the following:
- •Uncontrolled hypertension.
- •Gastrointestinal disorder affecting absorption.
- •Patients already included in another clinical trial involving an experimental drug.
研究组 & 干预措施
Arm A
The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.
干预措施: Leuprorelin Acetate 45Mg Powder for Injection Suspension Vial (Drug)
Arm A
The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.
干预措施: Goserelin Acetate 10.8 MG Subcutaneous Implant (Drug)
Arm A
The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.
干预措施: Triptorelin Pamoate (Drug)
Arm A
The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.
干预措施: Degarelix acetate (Drug)
Arm B
Patients will receive 6 cycles (each cycle is 30 days) of the study drug (4x 60mg tablets daily in a single intake).
干预措施: Apalutamide (Drug)
结局指标
主要结局
EPIC-26 sexual domain score
时间窗: 9 months after start of hormonal treatment
EPIC-26 sexual domain score (0 - 100 scale, with higher scores representing better sexual function)
次要结局
- FACT-P quality of life global score(9 months after start of hormonal treatment)
- EORTC QLQ C30 quality of life score(9 months after start of hormonal treatment)
- EORTC QLQ PR25 quality of life score(9 months after start of hormonal treatment)
- Grade of acute toxicity(After obtaining informed consent and up to 30 days after last dose)
- PSA response rates(0, 3, 6, and 9 months)