Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy

This open label, phase I/II non-randomised clinical trial will evaluate the dosimetry, efficacy and toxicity of Lu-PSMA in men with high PSMA-expressing high-risk localized or locoregional advanced prostate cancer (HRCaP) undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Patients will receive one or two cycles of 177Lu-PSMA followed by surgery. The primary objective is to determine the radiation absorbed dose in the prostate and involved lymph nodes. Secondary objectives include evaluating imaging response to therapy using PSMA-PET, biochemical response, pathological response, adverse effects of Lu-PSMA and surgical safety, and health-related Quality of Life (QoL).

Inclusion criteria

• Patient has provided written informed consent.
• Male patient aged 18 or over at the time of screening
• Histologically confirmed adenocarcinoma of the prostate, in a patient scheduled for RP and PLND with curative intent
• High or high-intermediate risk localised or locoregional prostate cancer (HRCaP) by European Association of Urology (EAU) criteria, including any of the following:

• PSA > 20 ng/mL
• ISUP grade group 3-5
• Clinical T-stage by digital rectal examination (DRE) of T2c or higher
• N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries)
• defined radiologically (CT/ MRI, or PSMA PET).
• High PSMA avidity on 68Ga-PSMA PET/CT, defined as an SUVmax of ≥ 20
• Normal baseline haematological function; haemoglobin 13.5-17.5g/dl), total white blood cell count (4-11 x 109/l), platelets (150-400 x 109/l), neutrophils (2-7.5 x 109/l) and lymphocytes (1-4 x 109/l)
• Normal baseline serum biochemistry; sodium 135-145 nmol/l, potassium 3.5-5 nmol/l, chloride 98-108 nmol/l, urea 3-9.2 nmol/l, creatinine 60-120μmol/l
• Willing and able to comply with all study requirements including all treatments and required assessments including follow up

Exclusion criteria

• Prostate cancer with significant neuroendocrine or other rare variant pathology
• Prior treatment for prostate cancer including radiotherapy and/or androgen deprivation therapy.
• Evidence of metastatic disease involving bone, viscera, or lymph nodes superior to the common iliac bifurcation based on CT, MRI, WBBS or PSMA PET/CT.
• Renal impairment [GFR < 60mL/min].
• Sjogren's syndrome.
• A history of or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.