Abiraterone/Prednisone + Standard ADT vs Standard ADT for Prostate Cancer Patients With PSMA-Positive Conventional Imaging Negative Pelvic Lymphadenopathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- 5-year failure-free survival rate
研究概览
简要总结
The advent of PSMA-PET has improved sensitivity and specificity in staging prostate cancer, particularly in intermediate- and high-risk disease. This has created uncertainty in the management of patients with PSMA-positive but conventionally negative pelvic lymphadenopathy (i.e., <1 cm in smallest diameter).
This study evaluates outcomes of enhanced androgen deprivation therapy (ADT) with abiraterone and prednisone compared to standard ADT, both in combination with radiation therapy, in patients with prostate cancer and PSMA-positive but conventionally negative pelvic lymphadenopathy.
A total of 140 eligible participants will be randomized to receive either enhanced ADT with abiraterone and prednisone or standard ADT, both with concurrent radiation therapy. Participants will be followed for 5 years after completion of ADT to assess outcomes.
The primary objective is to determine whether enhanced ADT improves 5-year failure-free survival compared to standard ADT. Secondary objectives include evaluation of toxicity, quality of life, biochemical progression-free survival, cancer-specific survival, overall survival, and metastasis-free survival.
Exploratory objectives include evaluation of tumor growth and regression rates using PSA values and assessment of the relationship between treatment outcomes and blood-based heme oxygenase-1 (HO-1) levels.
详细描述
The advent of PSMA-PET has allowed greater sensitivity and specificity when staging prostate cancers, particularly intermediate and high-risk prostate cancers. This has created a gap in knowledge regarding the treatment of patients who have PSMA-positive but conventionally negative pelvic lymphadenopathy (i.e. <1cm in smallest diameter). The purpose of this study is to compare outcomes of enhanced ADT with abiraterone and prednisone and standard ADT, both alongside radiation therapy, in prostate cancer patients with PSMA-positive but conventionally negative pelvic lymphadenopathy. We hypothesize that enhanced ADT with abiraterone and prednisone is superior to standard ADT for the treatment of prostate cancer patients with PSMA-positive but conventionally negative pelvic lymphadenopathy. We further hypothesize that standard ADT will be associated with a lower rate of adverse events. Patients will be followed for 5 years after completion of ADT to evaluate outcomes. The primary objective will be to determine if enhanced ADT has superior 5-year failure-free survival compared to standard ADT. Secondary objectives include evaluation of chronic toxicities, quality of life impact, biochemical progression-free survival, cancer-specific survival, overall survival, and metastasis-free survival.
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
- 30 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histopathologically proven diagnosis of local prostate cancer. Biopsies will be confirmed by UNMC pathology review if collected outside our institution.
- •Targetable PSMA-avid pelvic lymph node measuring <1cm in short axis diameter.
- •No prior definitive treatment or intervention received.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 within 14 days prior to registration.
- •Age ≥ 30 years.
- •Patient must be able to provide study-specific informed consent prior to study entry.
- •Patient must be able to swallow medications.
排除标准
- •Evidence of distant metastatic disease outside the pelvic lymph nodes (including osseous pelvic disease).
- •Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.
- •Relative or absolute contraindications to radiation therapy as determined by the treating physician. These include, but are not limited to, inflammatory bowel disease, connective tissue disorders (systemic lupus erythematosus, scleroderma, etc.), and genetic disorders that risk increased sensitivity to radiation therapy.
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months prior to registration.
- •Congestive heart failure (NYHA functional capacity class II or greater).
- •Transmural myocardial infarction within the last 3 months prior to registration.
- •History of stroke or transient ischemic attack within 3 months prior to registration.
- •Currently uncontrolled diabetes mellitus.
- •Ongoing arrhythmias of Grade >2 [National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE), version 5.03]; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
- •Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) in the past month.
- •Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
- •Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- •Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for Disease Control and Prevention definition that is being treated with contraindicated medications, including but not limited to Atazanavir, Saquinavir, Ritonavir, Indinavir, or Nelfinavir. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- •Uncontrolled seizures or seizures in the past 3 months. Patients can enroll if their seizures have been well-controlled for >3 months on antiseizure medications.
- •Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 5 grade 3 or greater within 30 days prior to registration.
- •History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration.
- •Total bilirubin ≥1.5X upper limit of normal (ULN) [except for subjects with Gilbert's disease, in which case total bilirubin not to exceed 10X ULN], alanine (ALT) and aspartate (AST) aminotransferase >= 2.5X ULN.
研究组 & 干预措施
Abiraterone/Prednisone + Standard ADT
Participants receive Abiraterone/Prednisone in addition to standard androgen deprivation therapy (ADT) in combination with radiation therapy
干预措施: Radiation Therapy (Radiation)
Standard ADT
Participants receive standard androgen deprivation therapy (ADT) in combination with radiation therapy.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Standard ADT
Participants receive standard androgen deprivation therapy (ADT) in combination with radiation therapy.
干预措施: Radiation Therapy (Radiation)
Abiraterone/Prednisone + Standard ADT
Participants receive Abiraterone/Prednisone in addition to standard androgen deprivation therapy (ADT) in combination with radiation therapy
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Abiraterone/Prednisone + Standard ADT
Participants receive Abiraterone/Prednisone in addition to standard androgen deprivation therapy (ADT) in combination with radiation therapy
干预措施: Prednisone (Drug)
Abiraterone/Prednisone + Standard ADT
Participants receive Abiraterone/Prednisone in addition to standard androgen deprivation therapy (ADT) in combination with radiation therapy
干预措施: Abiraterone (Drug)
结局指标
主要结局
5-year failure-free survival rate
时间窗: From randomization up to 5 years
Determine the impact of enhanced ADT with abiraterone/prednisone versus standard ADT on the 5-year failure-free survival of patients with PSMA-positive conventionally negative pelvic lymphadenopathy (i.e. \<1cm in smallest diameter).
5-year failure-free survival rate
时间窗: 7 years
Determine the impact of enhanced ADT with abiraterone/prednisone versus standard ADT on the 5-year failure-free survival of patients with PSMA-positive conventionally negative pelvic lymphadenopathy (i.e. \<1cm in smallest diameter).
次要结局
- Toxicity in both arms from 3 months to 2 years post-ADT.(From 3 months to 2 years post-ADT)
- Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (IPSS)(From 3 months to 2 Years post-ADT)
- Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (FACT-P)(From 3 months to 2 Years post-ADT)
- Evaluate local progression-free survival (i.e., failure-free survival excluding biochemical failure).(From randomization up to 5 years)
- Evaluate locoregional progression-free survival (i.e., failure-free survival excluding biochemical failure).(From randomization up to 5 years)
- Evaluate 5-year overall survival(From randomization up to 5 years)
- Evaluate 5-year cancer-specific survival(From randomization up to 5 years)
- Evaluate 5-year metastasis-free survival.(From randomization up to 5 years)
- Evaluate 5-year metastasis-free survival.(7-Years)
- Toxicity in both arms from 3 months to 2 years post-ADT.(4-years)
- Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (IPSS)(4-years)
- Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (FACT-P)(4-years)
- Evaluate local progression-free survival (i.e., failure-free survival excluding biochemical failure).(7-Years)
- Evaluate locoregional progression-free survival (i.e., failure-free survival excluding biochemical failure).(7-Years)
- Evaluate 5-year overall survival(7-Years)
- Evaluate 5-year cancer-specific survival(7-Years)