STEEL: A Randomized Phase II Trial of Salvage Radiotherapy With Standard vs Enhanced Androgen Deprivation Therapy (With Enzalutamide) in Patients With Post-Prostatectomy PSA Recurrences With Aggressive Disease Features
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 188
- 试验地点
- 108
- 主要终点
- Percentage of Participants Alive Without Progression (Progression-Free Survival)
研究概览
简要总结
Patients with post-prostatectomy PSA (Prostate Specific Antigen) recurrences with aggressive disease features will receive salvage radiation therapy and standard androgen deprivation therapy (ADT) or enhanced ADT to determine if there is any improvement in progression-free survival when enhanced ADT is used compared to standard ADT.
详细描述
PRIMARY OBJECTIVE:
To determine whether, in men with post-prostatectomy PSA (prostate specific antigen) recurrences with aggressive disease features, salvage radiotherapy (SRT) with enhanced androgen deprivation therapy (ADT), consisting of enzalutamide (MDV3100) and a GnRH analog, will improve progression-free survival compared to SRT with standard GnRH analog -based ADT.
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
- •Pathologically (histologically) proven adenocarcinoma confirmed by prostatectomy performed within 10 years prior to registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted.
- •Prostate-specific antigen (PSA) level (≥ 0.2 ng/mL) within 120 days prior to registration. Patients must have a PSA ≥ 0.2 ng/mL prior to starting ADT. For patients being followed by an ultrasensitive PSA assay, a serum PSA concentration of ≥ 0.10 ng/mL will be considered eligible.
- •GnRH analog may be started no more than 42 days prior study entry.
- •Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to registration.
- •Platelet count ≥ 75,000 x 10^9/µL independent of transfusion and/or growth factors within 90 days prior to registration.
- •At least 1 of the following aggressive features:
- •Gleason score of 8-10 (note any Gleason score is eligible)
- •Seminal vesicle invasion (SVI) (note any pT stage American Joint Committee on Cancer (AJCC) v8.0 is eligible but a pT stage
- •≥ pT3b is considered aggressive)
- •Locoregional node involvement at radical prostatectomy (RP) (pN1)
- •Persistently elevated PSA post-RP nadir (PEPP) defined as PSA > 0.1 ng/mL after radical prostatectomy
- •PSA ≥ 0.7 ng/mL
- •Serum albumin ≥ 3.0 g/dL within 90 days prior to registration
- •Glomerular filtration rate (GFR) ≥35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to registration.
- •Serum total bilirubin ≤1.5 × upper limit of normal (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 is eligible) within 90 days prior to registration.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN within 90 days prior to registration.
- •History and physical with Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 or within 90 days prior to registration.
排除标准
- •Definitive clinical or radiologic evidence of metastatic disease with the exception of locoregional lymph nodes.
- •Prior invasive malignancy (except non-melanomatous skin cancer carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years).
- •Prior systemic chemotherapy for the study cancer. Note: prior chemotherapy for a different cancer is allowable.
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- •History of any of the following:
- •Documented inflammatory bowel disease
- •Transmural myocardial infarction within the last 4 months prior to registration.
- •New York Heart Association Functional Classification III/IV within 4 months prior to registration.
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 4 months prior to registration
- •History of loss of consciousness or transient ischemic attack within 12 months prior to randomization
- •History of seizure disorder or condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
- •History of uncontrolled hypertension defined as a sustained systolic blood pressure in excess of 150 mmHg or a sustained diastolic blood pressure in excess of 90 mmHg despite optimized antihypertensive therapy.
- •History of repeated falls and fractures over the past 12 months that in the opinion of the treating investigator would put the patient at risk for poor bone outcomes from androgen receptor targeted therapy
- •Known gastrointestinal disorder affecting absorption of oral medications.
- •Active uncontrolled infection defined as an identified infectious condition that requires active therapy that has not yet been completed.
- •HIV positive patients with CD4 count < 200 cells/microliter within 30 days prior to registration OR HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. Note: HIV testing is not required for eligibility for this protocol as it is self-reported. This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive and/or interact with HAART.
研究组 & 干预措施
Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT)
Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: Radiation Therapy (Radiation)
Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT)
Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: Bicalutamide (Drug)
Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT)
Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: GnRH analog (Drug)
Salvage Radiation Therapy + Enhanced ADT
Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: Radiation Therapy (Radiation)
Salvage Radiation Therapy + Enhanced ADT
Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: Enzalutamide (Drug)
Salvage Radiation Therapy + Enhanced ADT
Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day).
SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.
干预措施: GnRH analog (Drug)
结局指标
主要结局
Percentage of Participants Alive Without Progression (Progression-Free Survival)
时间窗: From randomization to first failure or last known follow-up. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.
Progression-free survival (PFS) is estimated by the Kaplan-Meier method. PFS time is measured from randomization to the date of first PFS failure (biochemical or clinical failure, initiation of new unplanned anticancer treatment, or death from any cause) or last known follow-up (censored). Analysis was to occur after progression or death was reported for 101 participants. Biochemical failure is defined as first post-RT detectable PSA (PSA ≥ 0.05). Clinical failure is defined as either a local, regional, or distant failure.
次要结局
- Percentage of Participants With Biochemical Failure(From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.)
- Percentage of Participants With Alternative Biochemical Failure(From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.)
- Percentage of Participants With Hormone-refractory Disease(From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.)
- Percentage of Participants With Distant Metastasis(From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.)
- Percentage of Participants With Prostate Cancer Death(From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.)
- Percentage of Participants Alive (Overall Survival)(From randomization to death or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.)
- Change From Baseline to End of RT in the 5-level European Quality of Life Questionnaire (EQ-5D-5L) Index Score(Baseline and end of radiation treatment (RT). End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Change From Baseline to One Year After End of RT in the EQ-5D-5L Index Score(Baseline and one year after end RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Change From Baseline to Two Years After End of RT in the EQ-5D-5L Index Score(Baseline and two years after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Change From Baseline to End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score](Baseline and end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Change From Baseline to One Year After the End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score](Baseline and one year after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Change From Baseline to Two Years After the End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score](Baseline, two years after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Number of Participants by Highest Grade Adverse Event Reported CTCAE v5(From randomization to death or last known follow-up. Median follow-up time at the time of analysis was 33.1 months.)
- Number of Participants Any Adverse Event Occuring Within 30 Days Following the End of Treatment(From randomization to 30 days after the end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Number of Participants With Any Grade 3+ Adverse Event Occuring After 30 Days Following the End of RT(From 31 days after the end of RT to death or last known follow-up. Median follow-up was 33.1 months. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)
- Number of Participants With Post-baseline Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Scores ≥ 3(End of RT, one and two years after the end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.)