Phase I Study of Docetaxel and 177-Lutetium-PSMA-I&T in First-Line Treatment for Patients With Metastatic Castration-Resistant Prostate Adenocarcinoma
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).
• 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 1.
• 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.