PSMA-directed endoRadiothErapy of Castration-reSISTant Prostate Cancer (RESIST-PC). A Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 71
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events
研究概览
简要总结
This was an open-label, multicenter, prospective trial to assess safety and efficacy of 177Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer.
详细描述
Upon inclusion patients were randomized in a 1:1 ratio into two treatment doses. Radioligand therapy (RLT) were performed by repeated intravenous (i.v.) injection of 6.0 gigabecquerel (GBq) (+/- 10%) or 7.4 GBq (+/- 10%) 177Lu-PSMA-617 every 8+/- 1 weeks until reaching four cycles or threshold maximum dose to the kidneys of 23 Gray (Gy). All doses after labeling were presented in buffered solution for i.v. injection.
In the initial plan for the study design a total of 200 patients with histologically proven prostate cancer and metastatic castration-resistant prostate cancer (mCRPC) were to be enrolled, however due to early stopping of enrollment only 71 patients were enrolled at time of data base lock. Each patient underwent a screening visit within 14 days prior to receiving study drug. Treatment was continued until either of the following conditions applied:
- Prostate-specific antigen (PSA)/radiographic progression at >= 12 weeks
- Completion of four RLT cycles
- 23 Gy kidney dose would be exceeded by the next cycle as estimated by dosimetry
- Patient withdrawal (e.g. appearance of intolerable adverse events).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Prostate cancer proven by histopathology
- •Unresectable metastases
- •Progressive disease, both docetaxel naive and docetaxel treated.
- •Castration resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
- •Positive 68Ga-PSMA-11 PET/CT (positron emission computed tomography ) or diagnostic 177Lu-PSMA-617 scintigraphy
- •Sufficient bone marrow capacity as defined by WBC (white blood cell ) ≥2.500/μl, PLT (platelet) count ≥100.000/μl, Hb≥9.9 g/dl and ANC≥1500 mm3 for the first cycle and WBC≥2.000/ μl,PLT count ≥75.000/μl, Hb≥8.9 g/dl and ANC≥1000 mm3 for the subsequent cycles
- •Signing of the Informed Consent Form
- •Patients enrolling in this trail should have received either Enzalutamide or Abiraterone
排除标准
- •Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm) or other radionuclide therapy.
- •Glomerular Filtration Rate (GFR) <40 ml/min
- •Serum creatinine > 1.5 ULN
- •AST and ALT>5xULN
- •Urinary tract obstruction or marked hydronephrosis
- •Diffuse bone marrow involvement confirmed by super-scans
研究组 & 干预措施
177Lu-PSMA-617 (6.0 GBq)
Repeated i.v. application of 6.0 GBq (gigabequerel)(+/- 10%, arm 1) every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry
干预措施: 177Lu-PSMA-617 (Drug)
177Lu-PSMA-617 (7.4 GBq)
Repeated i.v. application of 7.4 GBq (gigabequerel)(+/- 10%, arm 2) of drug every 8+/- 1 weeks; RLT until reaching four cycles or threshold maximum dose to the kidneys of 23 Gy as determined by dosimetry
干预措施: 177Lu-PSMA-617 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events
时间窗: From first dosing (Day 0) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent, up to 24 months
Treatment-emergent adverse events (TEAEs) were collected from first dosing up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
Number of Participants Achieving PSA Response at Week 12
时间窗: Week 12
PSA response was defined as the proportion of patients who had a \>= 50% decrease in PSA from Baseline at Week 12.
次要结局
- Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status(Baseline, Treatment Visit 1, Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Follow-up Month 3, Follow-up Month 12, Follow-up Month 15)
- Percent Change in PSA From Baseline to Week 12(Week 12)
- Maximum Percent Change in PSA Response(Every 6 weeks during the treatment and every 3 (+/- 1) months after last treatment until reaching endpoint or 24 months after the first treatment)
- PSA Progression and Death Events(Date of randomization to the date of first documented PSA progression or death, whichever occurs first, reported between day of first patient randomized up to 24 months after the first treatment)
- RECIST 1.1 Disease Control Rate by Follow-up Assessment Visit(Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.)
- Prostate Cancer Working Group 3 (PCWG3) Bone Scan Clinical Impression by Visit(Screening, Week 8, Week 10, Week 16, Week 18, Week 22, Week 24, Follow-up Week 4, Follow-up Week 6, Follow-up Week 8)
- RECIST 1.1 Overall Response by Follow-up Assessment Visit(Before 3rd radioligand therapy (RLT) cycle, and then every 3 (+/- 1) months after last treatment dose until disease progression or 24 months after the first treatment dose.)
- Change From Baseline in Expanded Prostate Cancer Index Composite Short Form (EPIC-26)(Baseline, Month 3, Month 6, Follow-up Month 3)