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

NCT ID: NCT05269550

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-03
• Study Completion Date: 2028-12-15

Brief Summary

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).

Cohort extension: We hypothesize that integration of neoadjuvant androgen deprivation therapy will provide for pretreatment cancer downstaging and will allow us to achieve higher target doses to the imaging defined DILs than currently achieve. Additionally, we plan to include a novel sodium MRI protocol into the baseline imaging to compare DIL volumes delineated by this modality to those by mpMRI and PSMA PET and to characterize changes in sodium MRI in response to ADT alone and subsequent radiotherapy

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Men with high intermediate to very high risk prostate cancer

Men with high intermediate to very high risk prostate cancer

Group Type: EXPERIMENTAL

High-Intermediate Risk Patients-cohort 1

Intervention Type: RADIATION

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 end of radiotherapy (concurrent plus adjuvant)

High Risk or Very High-Risk Patients-cohort 1

Intervention Type: RADIATION

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 end of radiotherapy (concurrent plus adjuvant)

High-Intermediate Risk Patients-cohort 2

Intervention Type: RADIATION

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. Androgen deprivation therapy will commence 3 months before radiotherapy (concurrent plus adjuvant) and will continue for a total of 6 months.

High Risk or Very High-Risk Patients-cohort 2

Intervention Type: RADIATION

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. Androgen deprivation therapy will commence 3 months before radiotherapy (concurrent plus adjuvant) and will continue for a total of 18 months.

Interventions

High-Intermediate Risk Patients-cohort 1

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 end of radiotherapy (concurrent plus adjuvant)

Intervention Type: RADIATION

High Risk or Very High-Risk Patients-cohort 1

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 end of radiotherapy (concurrent plus adjuvant)

Intervention Type: RADIATION

High-Intermediate Risk Patients-cohort 2

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. Androgen deprivation therapy will commence 3 months before radiotherapy (concurrent plus adjuvant) and will continue for a total of 6 months.

Intervention Type: RADIATION

High Risk or Very High-Risk Patients-cohort 2

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. Androgen deprivation therapy will commence 3 months before radiotherapy (concurrent plus adjuvant) and will continue for a total of 18 months.

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Glenn Bauman

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

London Health Sciences Centre

London, Ontario, Canada

Sunnybrook Research Institute

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

ARGOS/CLIMBER

Identifier Type: -

Identifier Source: org_study_id