Cabazitaxel in Combination With 177Lu-PSMA-617 in Metastatic Castration-resistant Prostate Cancer

Inclusion Criteria

• •1. Male patients aged 18 years or older at the time of informed consent.
• •2. Patient has provided written informed consent.
• •3. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
• •4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• •5. Patients must have had prior treatment with docetaxel.
• •6. Patients must have progressed on a second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide) in the castrate-resistant setting.
• •7. Patients must have progressive disease. The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines this as any one of the following:
• •1. PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
• •2. Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
• •3. Bone progression: ≥ 2 new lesions on bone scan
• •8. At least three weeks since the completion of surgery prior to registration.
• •9. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
• •10. Serum testosterone levels ≤ 1.75nmol/L within 28 days prior to registration.
• •11. Imaging evidence of metastatic disease documented with either whole body bone scan (WBBS) or computed tomography (CT) scan performed within 28 days prior to registration.
• •12. Significant prostate-specific membrane antigen (PSMA) avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease.
• •13. Patients must have a life expectancy ≥ 12 weeks.
• •14. Assessed by a medical oncologist as suitable for treatment with cabazitaxel and 177Lu-PSMA-617.
• •15. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
• •1. Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last 28 days prior to registration)
• •2. Absolute neutrophil count (ANC) ≥ 1.5x10\^9/L
• •3. Platelets ≥ 150 x10\^9/L
• •4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
• •5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
• •6. Albumin ≥ 25 g/L
• •7. Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft-Gault equation
• •16. Sexually active patients are willing to use medically acceptable forms of barrier contraception.
• •17. Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.