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

Study Overview
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Brief Summary
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This 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)

Detailed Description
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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).

Official Title
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Study of the Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Radionuclide Therapy Prior to Radical Prostatectomy in Men With High-risk Localised Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: 177Lu-PSMA-617


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 177Lu-PSMA-617 followed by prostatectomy<br>177Lu-PSMA-617 followed by prostatectomy | Drug: 177Lu-PSMA-617<br>* Patients 1-10 will be given 5GBq of 177Lu-PSMA. Patients 11-20 will be given 2 cycles of 5GBq of 177Lu-PSMA, separated by 6 weeks.<br>* Other names: Lu-PSMA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the radiation absorbed dose in the prostate and involved lymph nodes following one or two administrations of Lu-PSMA in men with HRCaP prior to radical prostatectomy | Establishing the absorbed radiation dose in the prostate and involved lymph nodes (Gy) | Determined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the imaging response to therapy using PSMA-PET | PSMA PET response to therapy (complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease) | 6 weeks following final administration of Lu-PSMA | 
| To evaluate the biochemical response to therapy | PSA response | 6 weeks following final administration of Lu-PSMA | 
| To evaluate pathologic response in the prostate following prostatectomy | Pathological response (complete response, minimal residual disease) | After prostatectomy, approximately 6 weeks from final Lu-PSMA administration | 
| To evaluate toxicity of Lu-PSMA | Assessment of toxicity of Lu-PSMA using Common Terminology Criteria for Adverse Events (CTCAE) v5 | Until 8 weeks after prostatectomy | 
| To evaluate the surgical safety of prostatectomy following Lu-PSMA | Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications | Until 8 weeks after prostatectomy | 
| To evaluate overall health-related Quality of Life (QoL) | QoL indices will be scored using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire | baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years | 
| To evaluate prostate cancer health-related Quality of Life (QoL) | QoL indices will be scored using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire | baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years | 
| To evaluate patient function and bother after prostatectomy | Indices will be scored using the Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire | baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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177Lu-PSMA, Prostate Cancer, Radionuclide Therapy, Theranostics, prostate specific membrane antigen