177Lu-PSMA-I&T Prior to Radical Prostatectomy for Locally Advanced Disease

Study Overview
=================
Brief Summary
-----------------
Despite surgical advances, up to 50% of patients with high-risk locally advanced prostate cancer will die from their disease. Drug therapy before surgery has the potential to improve treatment success by lowering tumor volume in the prostate and treating small metastases. PET PSMA is an advanced imaging technique that allows the identification of areas involved by the tumor in the prostate or in the pelvis. This technique is based on the protein PSMA (prostate-specific membrane antigen) which is located on the tumor cells. The presence of PSMA on tumor cells has been recently used for treatment purposes. A chemical element (Lutetium) that binds to PSMA and emits local radiation can destroy tumors cells. This treatment has been used in patients with advanced metastatic disease and showed promising results. The investigators hypothesized that using these particles can improve long term results in patients who undergo surgery for prostate cancer which has not extensively spread. The investigators will assess both the immediate and long-term impact of this novel treatment.

Official Title
-----------------
177Lu-PSMA-I&T Radionuclide Neo-Adjuvant Treatment in Patients With Locally Advanced Prostate Cancer Prior to Radical Prostatectomy: Feasibility Trial.

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Radiation: 177Lu-PSMA-I&T Radionuclide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Male aged 18 years and older. 2. Patients were diagnosed with high risk localized prostate cancer (cT3/4 and/or Gleason score ≥8 and/or prostate biopsy or PSA ≥ 20 ng/dl) or loco-regional prostate cancer (pelvic lymphadenopathy of ≥2 cm on axial imaging). 3. High PSMA expression was confirmed. PET PSMA with tracer uptake greater than normal liver (maximal standardized uptake value ≥1.5 of liver). In addition, no PET FDG positive sites without high PSMA expression. 4. Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status score5 of 1 or lower and life expectancy of > 10 years. Exclusion Criteria: 1. Clinically significant impaired bone marrow defined by platelet count lower than 150×103/µl, white blood cells count lower than 4×103/µl, hemoglobin concentration lower than 12mg/dl. 2. Impaired liver function defined by albumin concentration lower than 3.5 gr/dl. 3. Impaired kidney function defined by glomerular filtration rate (GFR) lower than 40 mL/min. 4. Recent radiotherapy (within two months) 5. Concomitant usage of nephrotoxic drugs 6. Evidence of distant metastatic disease (distal lymphadenopathy, visceral or bone metastases).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant LuPSMA<br> | Radiation: 177Lu-PSMA-I&T Radionuclide<br>* Each patient will receive two single doses of 7.4 GBq 177-Lu-PSMA-I&T treatments. The treatments will be given intravenously, 2 weeks apart starting 12 weeks prior to radical prostatectomy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical safety | Surgical safety will be assessed according to the rate of intra- and post operative complications graded according to the clavien dindo classification. | 2 years | 
| Early oncological outcomes | Early oncological outcomes will be assessed according to the final surgical histology (e.g. stage , grade) and postoperative PSA | 2 years |