EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T: Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
研究概览
简要总结
This clinical trial will evaluate the safety and efficacy of [161Tb]Tb -PSMA-I&T in men with metastatic castration-resistant prostate cancer (mCRPC).
详细描述
This prospective, single-centre, single-arm phase I/II trial will assess the safety, efficacy and anti-tumour activity of [161Tb]Tb-PSMA-I&T in patients with mCRPC.
This study aims to assess and establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose (RP2D) of [161Tb]Tb-PSMA-I&T in patients with mCRPC.
42 men with mCRPC who have progressed with at least one line of taxane chemotherapy and at least one second-generation androgen receptor (AR)-targeted agent will be enrolled in this trial in two stages: dose escalation and a dose expansion phase over a period of 24 months.
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
- •Patient has provided written informed consent.
- •Male patients must be 18 years of age or older at the time of written informed consent.
- •Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum prostate specific antigen (PSA).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patients must have had prior treatment with at least one line of taxane chemotherapy, unless medically unsuitable.
- •Patients must have had prior treatment with at least one second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, apalutamide or darolutamide).
- •Patients must have progressive disease defined according to The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as any one of the following:
- •PSA progression - minimum of 2 rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
- •Soft tissue progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
- •Bone progression: ≥ 2 new lesions on bone scan
- •Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
- •Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL).
- •Significant prostate specific membrane antigen (PSMA) avidity on PSMA positron emission tomography (PET)/computed tomography (CT), defined as a minimum uptake of maximum standardised uptake value (SUVmax) 20 at a site of disease, and SUVmax > 10 at sites of measurable soft tissue disease ≥ 15mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
- •Patients must have a life expectancy ≥ 6 months.
- •Patients must have adequate bone marrow, hepatic and renal function, defined as:
- •Haemoglobin ≥ 100g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- •Platelets ≥ 150 x 10^9/L
- •Total bilirubin ≤ 1.5x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3x ULN if there is no evidence of liver metastasis or ≤ 5x ULN in the presence of liver metastases
- •Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40mL/min using the Cockcroft Gault equation (Appendix 3)
- •Sexually active patients are willing to use medically acceptable forms of barrier contraception.
- •Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.
- •At least 3 weeks since the completion of surgery or radiotherapy prior to registration.
排除标准
- •Prior treatment with another radioisotope (i.e. PSMA radioligands, radium-223, strontium-89, samarium-153).
- •Site(s) of discordant disease on PET imaging (Fluorodeoxyglucose [FDG]-positive and minimal PSMA-uptake).
- •Other malignancies (in addition to the prostate cancer being treated on this study) within the previous 2-years prior to registration other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
- •Symptomatic brain metastases or leptomeningeal metastases.
- •Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for more than 4 weeks.
- •Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
研究组 & 干预措施
Experimental: Treatment Arm
In this single-arm study, patients will receive doses of [161 Tb]Tb PSMA I&T on Day 1 of every 6 week Cycle. The dose of [161 Tb]Tb PSMA I&T will vary in dose-escalation. Up to 6 Cycles will be given.
干预措施: [ 161 Tb]Tb PSMA I&T (Drug)
结局指标
主要结局
Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
时间窗: Through study completion, up until 12 months after the last patient commences treatment
Safety of the combination will be measured by AEs and SAEs.
Maximum Tolerated dose (MTD)
时间窗: Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
The MTD is defined as the highest dose level at which the incidence of DLT was less than 1/3 or 2/6.
Dose Limiting toxicities (DLTs)
时间窗: Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
A DLT is defined as a toxicity that prevents further administration of the trial treatment at that dose level. Each cohort of 3 patients will be assessed for DLTs after 6 weeks from administration of cycle 1.
Recommended Phase 2 Dose (RP2D)
时间窗: Up to 30 months from the time the first patient is recruited.
After the MTD is established, additional patients will be treated at the MTD. Safety and efficacy data from the study will be used to define the RP2D.
次要结局
- Health-related quality of life (HR-QoL)(Through completion of 12 months after treatment commencement of last patient)
- Radiographic Progression-Free Survival (rPFS)(Through study completion, up until 12 months after the last patient commences treatment)
- Absorbed radiation dose(On Day 4 of Cycle 1 (each Cycle is 42 days))
- 50% Prostate-Specific Antigen Response Rate (PSA-RR)(Through study completion, up until 12 months after the last patient commences treatment or until PSA progression)
- PSA progression free survival (PSA-PFS)(Through study completion, up until 12 months after the last patient commences treatment or until PSA progression)
- Progression free survival (PFS)(Through study completion, up until 12 months after the last patient commences treatment or until PSA progression)
- Overall survival (OS)(Through study completion, up until 12 months after the last patient commences treatment)
- Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST1.1) in patients with measurable disease(Through study completion, up until 12 months after the last patient commences treatment)
- Describe worst pain within 24 hours of Brief Pain Inventory-Short Form (BPI-SF) completion(Pain will be assessed at baseline, then at 6, 12, 24, 36 and 48 weeks)