Phase I Study of Docetaxel and 177-Lutetium-PSMA-I&T in First-Line Treatment for Patients With Metastatic Castration-Resistant Prostate Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Recommended Phase II Dose (RP2D) of docetaxel in combination with 177Lu-PSMA-I&T
研究概览
简要总结
This is a Phase I, open-label, single-center study evaluating the safety, tolerability, and recommended Phase II dose of docetaxel when combined with a fixed dose of 177-Lutetium-PSMA-I&T in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Patients will receive standard androgen deprivation therapy, docetaxel at escalating doses (50 mg/m², 60 mg/m², 75 mg/m² every 3 weeks), and 177Lu-PSMA-I&T at a fixed dose of 7.4 GBq every 6 weeks (up to 4 cycles). A 3+3 dose escalation design will be employed. Secondary endpoints include safety profile, treatment-limiting toxicities, treatment completion rate, and delayed toxicity. Exploratory endpoints include PSA response, radiographic progression-free survival (rPFS), and PERCIST-based response rate.
详细描述
This is a Phase I, open-label, single-center study designed to evaluate the safety, tolerability, and to determine the recommended Phase II dose (RP2D) of docetaxel when combined with a fixed dose of 177Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC) who have not previously received chemotherapy for castration-resistant disease.
All participants will continue receiving androgen deprivation therapy (ADT) throughout the study. The treatment regimen includes docetaxel administered intravenously every 3 weeks at escalating doses of 50 mg/m², 60 mg/m², and 75 mg/m² (up to 10 cycles), combined with 177Lu-PSMA-I&T at a fixed dose of 7.4 GBq every 6 weeks, for up to 4 cycles. A traditional 3+3 dose-escalation design will be used, allowing sequential patient enrollment and assessment of dose-limiting toxicities (DLTs) during the first 3 weeks to establish the optimal docetaxel dose for future studies.
Treatment will continue until completion of 10 cycles of docetaxel and 4 cycles of 177Lu-PSMA-I&T, or until disease progression, unacceptable toxicity, or withdrawal of consent. Imaging exams, including SPECT, will be performed after each lutetium administration for dosimetry assessment.
The primary endpoint is the determination of the RP2D of docetaxel when combined with 177Lu-PSMA-I&T. Secondary endpoints include evaluation of the overall safety profile, incidence of DLTs, treatment completion rate, and monitoring of late toxicities. Exploratory endpoints include PSA response (≥50% decline), radiographic progression-free survival (rPFS), and response rate based on PERCIST criteria using PSMA-PET.
Patients will undergo imaging assessments every 6 weeks (±7 days), including PSMA-PET/CT, FDG-PET/CT, CT scans, and bone scintigraphy. Laboratory tests will be performed every 3 weeks during treatment and every 6 weeks during the post-treatment follow-up, for up to 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Men aged 18 years or older.
- •Histological or cytological diagnosis of prostate adenocarcinoma. The presence of intraductal or cribriform carcinoma will be allowed.
- •Presence of metastatic disease on conventional imaging exams (bone scintigraphy and/or CT scan or MRI).
- •Patients with castration-resistant disease, defined as testosterone <50 ng/mL in the context of prior orchiectomy or ongoing androgen deprivation therapy (ADT) with LHRH agonists or antagonists, plus at least one of the criteria below:
- •PSA ≥2.0 ng/mL with at least two consecutive PSA rises at intervals of at least 1 week.
- •Radiologic progression defined by the investigator.
- •Clinical progression defined by the investigator.
- •Performance status per the Eastern Cooperative Oncology Group (ECOG) equal to 0 or
- •Willingness to continue ongoing ADT.
- •Adequate organ function as defined below:
- •Parameter Requirement
- •Neutrophils ≥ 1,500/µL
- •Hemoglobin ≥ 12 g/dL
- •Platelets ≥ 100,000/µL
- •Creatinine ≤ 1.5 x upper limit of normal
- •Potassium > 3.5 mmol/L and <5.0 mmol/L
- •Total Bilirubin ≤ ULN (unless Gilbert's disease)
- •AST (TGO) ≤ 2.5 x ULN
- •ALT (TGP) ≤ 2.5 x ULN
- •68Ga-PSMA-PET/CT performed during the screening phase showing metastatic (extraprosthetic and extrapelvic) disease with radiotracer uptake and:
- •SUVmax ≥20 in at least one site;
- •SUVmax >10 in all other measurable metastatic sites.
- •Lesions with uptake at least 1.5 times greater than hepatic background will be considered measurable.
排除标准
- •Presence of any small-cell or neuroendocrine component of prostate carcinoma.
- •Prior receipt of chemotherapy or radiopharmaceuticals in the castration-resistant setting.
- •Presence of another active malignancy requiring treatment or a cancer diagnosis within the past 5 years. Carcinoma in situ of any site, squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or papillary bladder tumors will be allowed if previously treated.
- •Severe urinary incontinence at the investigator's discretion.
- •18F-FDG-PET/CT will be performed during screening and will be considered exclusionary if there is discordance with the 68Ga-PSMA-PET/CT. Discordance is defined as FDG-hypermetabolic lesions with absent or low PSMA uptake (SUVmax <10) in more than 50% of measurable metastatic lesions.
- •Patients with brain metastases visible on 68Ga-PSMA-PET/CT.
研究组 & 干预措施
Docetaxel 50 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 50 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: Docetaxel 50mg/m2 (Drug)
Docetaxel 50 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 50 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: 177Lu-PSMA-I&T (Radiation)
Docetaxel 60 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 60 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: Docetaxel 60mg/m2 (Drug)
Docetaxel 60 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 60 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: 177Lu-PSMA-I&T (Radiation)
Docetaxel 75 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 75 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: 177Lu-PSMA-I&T (Radiation)
Docetaxel 75 mg/m² + 177Lu-PSMA-I&T
Patients will receive docetaxel 75 mg/m² IV every 3 weeks plus 177Lu-PSMA-I&T 7.4 GBq IV every 6 weeks. all patients will continue androgen deprivation therapy.
干预措施: Docetaxel 75 mg/m² (Drug)
结局指标
主要结局
Recommended Phase II Dose (RP2D) of docetaxel in combination with 177Lu-PSMA-I&T
时间窗: First 3 weeks
Determination of the recommended Phase II dose using a standard 3+3 dose-escalation design.
次要结局
- Overall safety profile (CTCAE v5.0)(Up to 24 weeks)
- Incidence of dose-limiting toxicities (DLTs)(first 3 weeks.)
- Treatment completion rate(Up to 24 weeks)
- Incidence of late toxicities(Up to 24 weeks post-treatment)