A Multi-Center Trial of Androgen Suppression With Abiraterone aCetate, LEuprolide, PARP Inhibition and Stereotactic Body Radiotherapy (ASCLEPIuS): A Phase I/2 Trial in High Risk and Node Positive Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 12
- 主要终点
- Dose-limiting toxicities (Phase 1)
研究概览
简要总结
The purpose of this study is to establish the maximum tolerable dose of niraparib when combined with prostate stereotactic body radiotherapy (SBRT), abiraterone, leuprolide, and prednisone (the phase 1 portion of the study) and determine 3-year biochemical PSA recurrence free-survival with this treatment approach (the phase 2 portion of the study).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Pathologic biopsy proven adenocarcinoma of the prostate
- •At least one of the following criteria:
- •cN1 on conventional or PET imaging
- •Grade group 5
- •Grade group 4
- •Grade group 3 and PSA ≥20 ng/mL
- •High probability of Radiographic T3 on MRI AND Grade group ≥2
- •Grade Group 3 AND PSA ≥10 ng/mL AND ≥50% positive biopsy cores
- •Adequate organ and marrow function as defined per protocol.
- •Use of highly effective contraception (e.g. condoms) for the duration of treatment and a minimum of 120 days thereafter. Men must also agree not to donate sperm for the duration of the study participation, and for at least 120 days thereafter.
- •International Prostate Symptoms Score (IPSS) ≤ 20
- •Medically fit for treatment and agreeable to follow-up
- •Ability to understand and the willingness to sign a written informed consent
- •Tissue available for MiOncoSeq testing to assign DNA repair deficiency status
排除标准
- •Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
- •Clinical or radiographic evidence of high probability of clinical T4 disease
- •Prostate gland size >80 cc measured by ultrasound or MRI
- •Prominent median lobe assessed by treating physician
- •Lack of tissue from biopsy to be sent for correlative studies
- •Any prior treatment for prostate cancer (incudes history of TURP within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy)
- •Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
- •Prohibited 3 months before participant registration and during administration of study treatment: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide), steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals.
- •History of prior pelvic radiation therapy
- •Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital
- •Enrollment concurrently in another investigational drug study within 1 month of registration
- •History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer
- •History of or active Crohn's disease or ulcerative colitis
- •Contraindication to or inability to tolerate MRIs
- •Patients with severe depression
- •Uncontrolled diabetes or known HbA1c>10
- •Any gastrointestinal disorder affecting absorption
- •Active pituitary or adrenal dysfunction
- •Patients with significant cardiovascular disease potentially including severe / unstable angina, recent history of myocardial infarction, clinically significant heart failure, cerebrovascular disease, venous thromboembolic events, clinically significant arrhythmias)
- •Uncontrolled hypertension with persistently elevated systolic blood pressure >160 mmgHg or diastolic blood pressure >100 mmHg despite anti-hypertensive agents.
- •Prolonged QTc >450 ms or any ECG changes that interfere with QT interval interpretation
- •Major surgery within 1 month of registration
- •History of myelodysplastic syndrome or leukemia
- •A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or prednisone
- •Active infection or other medical condition that would be a contraindication to prednisone use
- •Patients with known active hepatitis or chronic liver disease including cirrhosis
- •Any condition that in the opinion of the investigator would preclude participation in this study
研究组 & 干预措施
Niraparid Dose Escalation
Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.
干预措施: Stereotactic body radiotherapy (SBRT) (Radiation)
Niraparid Dose Escalation
Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.
干预措施: Niraparib (Drug)
Niraparid Dose Escalation
Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.
干预措施: Leuprolide (Drug)
Niraparid Dose Escalation
Dose Level 1: 100 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 2: 200 mg PO daily of Niraparib but held for 5 days (+/- 2 days) prior to RT, during SBRT, and 5 days (+/- 2 days) after last fraction of SBRT
Dose Level 3: 200 mg PO daily of Niraparib without breaks during SBRT until completion of 6 cycles.
干预措施: Abiraterone Acetate (Drug)
结局指标
主要结局
Dose-limiting toxicities (Phase 1)
时间窗: Up to 112 days after initial dose of niraparib
The proportion of patients at each dose level with dose-limiting toxicity (DLT), defined as any treatment related grade 3-5 adverse event experienced within the first 4 treatment cycles (112 days), assessed per NCI's CTCAE version 5.0.
Proportion of patients experiencing biochemical failure
时间窗: Up to 3 years after first dose of niraparib
Change in PSA level from the beginning of study treatment for up to 3 years later will determine the biochemical failure rate. Biochemical failure will be defined using the Phoenix definition of the PSA nadir + 2 ng/mL.
次要结局
- Proportion of patients with undetectable post-treatment PSA(Measured during the end of the 6th cycle of therapy (during week 24 +/- 7 days))
- Prostate cancer specific survival(Up to 5 years after first dose of niraparib)
- Overall survival(Up to 5 years after first dose of niraparib)
- Change in health related quality of life(From baseline up to 3 years after last dose of niraparib)
- Proportion of patients with distant metastases(Up to 5 years after first dose of niraparib)