Multicenter Randomized Trial of 68Ga-PSMA-11 PET/CT Based SRT After Radical Prostatectomy

Study Overview
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Brief Summary
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This phase III trial studies how well Gallium Ga 68-labeled PSMA-11 (68Ga-PSMA-11) positron emission tomography (PET)/computed tomography (CT) works in diagnosing participants with prostate cancer that has come back after surgery. 68Ga-PSMA-11 are taken up by cancer cells. Diagnostic procedures, such as PET/CT scans, may help find and diagnose prostate cancer and find out how far the disease has spread. Giving 68Ga-PSMA-11 with PET/CT may help doctors plan better for salvage radiation therapy in participants with recurrent prostate cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. Success rate of salvage radiation therapy (SRT) measured as biochemical progression-free survival after initiation of SRT. SECONDARY OBJECTIVES: I. Sub-group analysis of the primary endpoint (success rate of SRT) within the subgroup with baseline PSA ≥ 0.5 ng/ml II. 5-year biochemical progression-free survival rate (from date of randomization). III. Metastasis free survival. IV. Initiation of additional salvage therapy after completion of SRT. V. Change in initial treatment intent. OUTLINE: Participants are randomized to 1 of 2 arms. ARM I: Participants receive standard of care SRT. ARM II: Participants receive 68Ga-PSMA-11 intravenously (IV) and 50-100 minutes later undergo whole-body (skull base to mid-thighs) PET/CT. Participants then undergo SRT per the discretion of the treating radiation oncologist. After conclusion of PET/CT, participants are followed up periodically for up to 5 years.

Official Title
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Phase III Randomized Multicenter Trial of 68Ga-PSMA-11 PET/CT Molecular Imaging for Prostate Cancer Salvage Radiotherapy Planning [PSMA-SRT]

Conditions
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Recurrent Prostate Carcinoma

Intervention / Treatment
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* Other: Best Practice
* Procedure: Computed Tomography
* Radiation: Gallium Ga 68-labeled PSMA-11
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathology proven prostate cancer. Planned SRT for recurrence after primary prostatectomy. Prostate-specific antigen (PSA) >= 0.1 ng/ml at time of enrollment. Willingness to undergo radiotherapy. Treating radiation oncologist intends to incorporate 68Ga-PSMA-11 PET/CT findings into the radiotherapy plan if patient undergoes 68Ga-PSMA-11 PET/CT. Exclusion Criteria: Extra-pelvic metastasis on any imaging or biopsy. Androgen deprivation therapy (ADT) within 3 months before 68Ga-PSMA-11 PET/CT. Contraindications to radiotherapy (including active inflammatory bowel disease). Concurrent systemic therapy for prostate cancer with investigational agents.
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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (standard of care)<br>Participants receive standard of care SRT. | Other: Best Practice<br>* Undergo standard of care<br>* Other names: standard therapy;|
| Experimental: Arm II (68Ga-PSMA-11 PET/CT)<br>Participants receive 68Ga-PSMA-11 IV and 50-100 minutes later undergo whole-body (skull base to mid-thighs) PET/CT. Participants then undergo SRT per the discretion of the treating radiation oncologist. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Radiation: Gallium Ga 68-labeled PSMA-11<br>* Given IV<br>* Other names: PSMA-HBED-CC GA-68;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of salvage radiation therapy (SRT) | Will be measured as biochemical progression-free survival after initiation of SRT. Will use a log rank test to compare progression free survival time between the two randomized treatment arms. | From date of initiation of SRT assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical progression-free survival rate | Will utilize Cox-proportional hazards regression models. These models will include terms for treatment as well as appropriate clinical/demographic covariates (e.g., androgen deprivation therapy [ADT], pelvic lymph node radiation therapy [LN RT], prostate specific antigen [PSA] doubling time, Gleason grade, T stage, age, etc). Residual analyses will be performed to evaluate the proportional hazards assumptions of the Cox model. As a sensitivity analysis, we will also consider survival models that can account for competing risks (ex. death from other causes). | From date of randomization assessed up to 5 years | 
| Metastasis free survival | Will utilize Cox-proportional hazards regression models. These models will include terms for treatment as well as appropriate clinical/demographic covariates (e.g., ADT, pelvic LN RT, PSA doubling time, Gleason grade, T stage, age, etc). Residual analyses will be performed to evaluate the proportional hazards assumptions of the Cox model. As a sensitivity analysis, we will also consider survival models that can account for competing risks (ex. death from other causes). | Up to 5 years | 
| Initiation of additional salvage therapy after completion of SRT | Will utilize Cox-proportional hazards regression models. These models will include terms for treatment as well as appropriate clinical/demographic covariates (e.g., ADT, pelvic LN RT, PSA doubling time, Gleason grade, T stage, age, etc). Residual analyses will be performed to evaluate the proportional hazards assumptions of the Cox model. As a sensitivity analysis, we will also consider survival models that can account for competing risks (ex. death from other causes). | Up to 5 years | 
| Change in initial treatment intent | Will utilize Cox-proportional hazards regression models. These models will include terms for treatment as well as appropriate clinical/demographic covariates (e.g., ADT, pelvic LN RT, PSA doubling time, Gleason grade, T stage, age, etc). Residual analyses will be performed to evaluate the proportional hazards assumptions of the Cox model. As a sensitivity analysis, we will also consider survival models that can account for competing risks (ex. death from other causes). | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSMA, PET/CT, salvage radiation therapy, randomized trial