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

Prior treatment

• 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.

Other

• Presence of any small-cell or neuroendocrine component of prostate carcinoma.
• 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.

• 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.