PSMA MRI Guided Prostate SBRT (ARGOS)/Comprehensive, Longitudinal Evaluation of Imaging Biomarkers Post Radiotherapy (CLIMBER)

Study Overview
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Brief Summary
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This study is a prospective Phase I/II protocol enrolling men with either high intermediate-risk or high-risk or very high-risk prostate cancer. All men will have PSMA Targeted PET (using the PSMA targeting ligand PSMA 1007) and multiparametric magnetic resonance imaging (mpMRI) for delineation of intra-prostatic foci of cancer and any involved regional lymph nodes based on high SUV uptake on PET or mpMRI (T2W, DWI/ADC, DCE) appearance suspicious for cancer. Tumour delineation will be performed by fusing the PSMA PET and mpMRI with planning CT simulation images. Fiducial marker implantation for treatment guidance will be mandatory but use of other organs at risk protection strategies (i.e. GU Loc, Space-OAR) will be allowed but not mandatory. Patients will be treated with image-guided SBRT using the fiducial markers for intra-fraction motion management. Dose escalation to imaging defined targets (intra-prostatic and involved nodes on PSMA PET + MRI) will be accomplished through a simultaneous boost technique. Maintaining dose to organs at risk will take precedence over boost dose targets (targeted maximum dose of 50Gy/5 fractions to imaging defined prostatic lesion; 35Gy/5 fractions to imaging defined involved nodes).

Official Title
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PSMA MRI Guided Prostate SBRT(ARGOS)/Comprehensive, Longitudinal Evaluation of Imaging Biomarkers Post Radiotherapy (CLIMBER)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: High Intermediate Risk Patients
* Radiation: High Risk or Very High-Risk Patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years of age Histologically confirmed carcinoma of the prostate High-intermediate risk or high risk as defined by NCCN criteria: High intermediate: 2 or 4 intermediate risk factors (T2B-T2C, Gleason GG 2 or 3, PSA 10-20) or GG 3 or intermediate risk with equal or >50% biopsy core involvement High-risk: one of T3a, Gleason GG 4 or 5, or PSA >20 ng/ml Very-high risk: one of primary Gleason Pattern 5, >4 cores Grade Group 4 or 5, clinical T3b, or more than 1 high-risk feature Conventional imaging (bone scan and abdominal pelvic computed tomography) negative for extra-pelvic nodal, skeletal or visceral metastases Willing to give informed consent to participate in this clinical trial Able and willing to complete EPIC questionnaires Exclusion Criteria: Prior prostate cancer treatment (apart from prior 5-alpha reductase inhibitor treatment); androgen deprivation therapy prior to enrollment or treatment planning not permitted Men with clinical T4 disease are excluded Contraindication to radical prostate radiotherapy e.g. connective tissue disease or inflammatory bowel disease Contraindication to prostate MRI (i.e. non0compatible stent, pacemaker, prosthesis, etc.) Contraindication to use of PSMA PET agent PSMA 1007 due to intolerance or allergy Anticoagulation medication (if unsafe to discontinue for gold seed insertion) Diagnosis of bleeding diathesis Poor baseline urinary function defined as a score of 5 (big problem) on question 5 of the EPIC 26 (Overall, how big a problem has your urinary function been for you during the last 4 weeks?) Definitive extra-pelvic nodal or distant metastatic disease on conventional staging investigations

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: Men with high intermediate to very high risk protstate cancer<br> | Radiation: High Intermediate Risk Patients<br>* Patients will receive 35Gy/5 fractions to the whole prostate (25 Gy to proximal Seminal Vesicles) with a simultaneous boost to PET/MRI defined intra-prostatic foci to a target maximum dose of 50Gy/5 fractions. Six months of androgen deprivation therapy will commence with the start of radiotherapy (concurrent plus adjuvant)<br>Radiation: High Risk or Very High-Risk Patients<br>* Patients will receive 35Gy/5 fractions to the whole prostate (25Gy to whole Seminal Vesicles) with a simultaneous boost to PET/MRI defined intra-prostatic foci to a target maximum dose of 50Gy/5 fractions. Pelvic lymph nodes will receive 25Gy/5 fractions synchronous with prostate treatment with a simultaneous boost to imaging involved nodes to a maximum of 35Gy/5 fractions. Eighteen months of androgen deprivation therapy will commence with the start of radiotherapy (concurrent plus adjuvant)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Toxicity | 6-month gastrointestinal (GI) and genitourinary (GU) toxicity using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). | 6-months | 
| 6-week Toxicity | 6-week gastrointestinal (GI) and genitourinary (GU) toxicity using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). | 6-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | Quality of life measured by the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaires. | 5 years | 
| Disease Free Survival | Five-year disease-free survival (DFS) as a composite of biochemical control, patient death or development of clinical metastases or institution of salvage ADT. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High intermediate risk prostate cancer, High-risk prostate cancer