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.
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).
PSA ≥2.0 ng/mL with at least two consecutive PSA rises at intervals of at least 1 week.
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.
Sequential
Docetaxel 50mg/m2
DrugIntravenous, 50 mg/m², every 3 weeks, up to 10 cycles
Docetaxel 60mg/m2
DrugIntravenous, 60 mg/m², every 3 weeks, up to 10 cycles
Docetaxel 75 mg/m²
DrugIntravenous, 75 mg/m², every 3 weeks, up to 10 cycles
177Lu-PSMA-I&T
RadiationIntravenous administration at a fixed dose of 7.4 GBq every 6 weeks, up to 4 cycles.
Recommended Phase II Dose (RP2D) of docetaxel in combination with 177Lu-PSMA-I&T
Determination of the recommended Phase II dose using a standard 3+3 dose-escalation design.
Incidence of dose-limiting toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs)
Overall safety profile (CTCAE v5.0)
Overall safety profile (CTCAE v5.0)
Treatment completion rate
Treatment completion rate (≥4 doses of lutetium and ≥7 doses of docetaxel)
Incidence of late toxicities
Incidence of late toxicities
PSA50 response rate
PSA50 response rate (≥50% decline from baseline)
Radiographic progression-free survival (rPFS) per PCWG3
Radiographic progression-free survival (rPFS) per PCWG3
PERCIST-based response rate via PSMA-PET
PERCIST-based response rate via PSMA-PET
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