TheraP: A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (ANZUP Protocol 1603)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 201
- 试验地点
- 11
- 主要终点
- Prostate Specific Antigen response rate (PSA RR)
研究概览
简要总结
This open label, randomised, stratified, 2-arm, multicentre, phase 2 trial aims to determine the activity and safety of Lu-PSMA vs cabazitaxel in men with progressive metastatic castration resistant prostate cancer
详细描述
Despite recent advances in the treatment of prostate cancer, metastatic disease remains incurable.
Prostate specific membrane antigen (PSMA) is present in high quantities on the cell surface of prostate cancers, and is also further increased in metastatic hormone refractory carcinomas. PSMA is an attractive target for both imaging and treatment of prostate cancer. PSMA bound to the radioactive substance Gallium68 (GaPSMA) is rapidly being adopted for imaging prostate cancer using positron emission tomography (PET) scanning.
Radionuclide therapy is an approach for the treatment of cancer that uses tumour targeting agents to deliver high doses of radiation to sites of tumours. The PSMA molecule used for PET imaging can also be labelled with Lutetium177 (Lu177), a radioactive substance.
The aim of this study is to determine the activity and safety of LuPSMA radionuclide therapy.
Patients with metastatic prostate cancer who have progressed despite hormonal therapy and chemotherapy, will be randomised to receive either LuPSMA radionuclide therapy (up to a maximum of 6 cycles of therapy) or cabazitaxel chemotherapy (up to a maximum of 10 cycles of therapy).
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
- •Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
- •Documented histopathology of prostate adenocarcinoma OR
- •Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes)
- •Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog
- •Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL
- •Target or non-target lesions according to RECIST 1.1
- •Prior treatment with docetaxel
- •Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
- •ECOG Performance status 0 to 2
- •Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel
- •Adequate renal function:
- •Cr Cl ≥ 40mL/min (Cockcroft-Gault formula)
- •Adequate bone marrow function:
- •Platelets ≥ 100 x10 billion /L
- •Hb ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
- •Neutrophils > 1.5 x10 billion/L
- •Adequate liver function:
- •Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5-2x ULN, must have a normal conjugated bilirubin)
- •AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
- •Estimated life expectancy > 12 weeks
- •Study treatment both planned and able to start within 21 days of randomisation
- •Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments
- •Signed, written informed consent
排除标准
- •Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
- •Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10
- •Sjogren's syndrome
- •Prior treatment with cabazitaxel or Lu-PSMA
- •Contraindications to the use of corticosteroid treatment
- •Active malignancy other than prostate cancer
- •Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
- •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
- •Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
研究组 & 干预措施
177Lu-PSMA617
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles.
The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.
干预措施: 177Lu-PSMA617 (Other)
Cabazitaxel
Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles.
Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.
干预措施: Cabazitaxel (Drug)
结局指标
主要结局
Prostate Specific Antigen response rate (PSA RR)
时间窗: Through study completion, on average 4 years
PSA RR defined as the proportion of participants in each group with a PSA reduction of ≥ 50% from baseline.
次要结局
- Objective Tumour Response Rate(Through study completion, on average 4 years)
- PSA progression free survival(Through study completion, on average 4 years)
- Radiographic progression free survival(Through study completion, on average 4 years)
- Overall survival(Through study completion, on average 4 years)
- Frequency and severity of adverse events(From first study dose to 12 weeks after completing study treatment)
- Pain progression free survival(Through study completion, on average 4 years)
- Pain Response (PPI and Analgesic Score)(Through study completion, on average 4 years)
- Progression free survival(Through study completion, on average 4 years)
- Health-related quality of life(Through study completion, on average 4 years)