PSMA Response in Metastasized Hormone Sensitive Prostate Cancer - Enzalutamide

Study Overview
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Brief Summary
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PSMA-PET/CT response measurements after LHRH agonist and upfront enzalutamide therapy in men diagnosed with de novo metastasized hormonal sensitive prostate cancer.

Detailed Description
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Rationale: Men, newly diagnosed with metastasized prostate cancer on PSMA PET/CT, who start on standard hormonal therapy, are additionally treated with either upfront chemotherapy or upfront extra androgen-receptor targeted agents ('ARTA'), as per guidelines' recommendations. The benefit in overall survival of these two options is similar, but important differences exist in patient-specific efficacy, costs, side-effects, and impact on quality of life. No predictive factors are available to individualize treatment choice. Currently, a one-size-fits-all strategy with hormonal therapy plus chemotherapy is usually followed. Objective: To assess the predictive value of early response measurements on PSMA-PET/CT for therapy success, defined as time to development of castration-resistant prostate cancer (CRPC), in order to personalize treatment choice. Study design: Prospective, single arm, open label, non-interventional, non-therapeutic observational cohort study. Study population: Patients >18 years with newly diagnosed, histologically proven prostate cancer with >3 skeletal or visceral metastatic lesions on the PSMA-PET/CT, who are considered eligible for upfront therapy (enzalutamide) in addition to standard hormonal therapy. Main study parameters/endpoints: Primary parameter: Predictive value of early response on PSMA-PET/CT to upfront therapy, according to PERCIST criteria. Primary endpoint: Time to development of CRPC. Secondary parameters: Predictive value of early response on PSMA-PET/CT to hormonal therapy; predictive value of baseline PSMA-PET/CT, analysis of response in different subgroups of patients: e.g. high versus low tumour load, high versus low PSA, high versus low Gleason score. Secondary endpoint: Time to initiation of second line therapy after castration-resistant disease has been found. Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Patients will be treated according to standard of care, including baseline PSMA-PET/CT. The timing of follow-up PSMA-PET/CT imaging will be standardized. Instead of imaging at biochemical or clinical signs of disease progression, one PSMA-PET/CT will be performed after two months of hormonal therapy, one PSMA-PET/CT will be performed after two months of upfront therapy. Each PSMA-PET/CT scan will require an extra visit (2-3 hours) and a limited radiation burden after intravenous injection of PSMA. The additional information from the standardized follow-up PSMA-PET/CT scans will not be used for clinical decision-making.

Official Title
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Individualisation of Management With Novel Upfront Therapies in Newly Diagnosed Metastasized Prostate Cancer Using (PSMA)PET/CT Imaging - Enzalutamide

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: PSMA-PET/CT response evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men >18 years of age. Mentally competent and understanding of benefits and potential burden of the study. Written and signed informed consent. Histological confirmed diagnosis of adenocarcinoma of the prostate. Indicated to start on hormonal therapy (any LHRH agonist or antagonist). Indicated to start on upfront therapy (enzalutamide). Any initial PSA. Any Gleason score. Any T-stage. Any N-stage. Stage M1, with multiple / high volume metastasis: More than three (>3) metastatic lesions (any combination of either lymph node metastasis outside of pelvis, bone metastasis, or visceral metastasis), as seen on PSMA-PET/CT-imaging. As these patients are treated with palliative intent. Exclusion Criteria: Concomitant malignancy (except from BCC of the skin). History of prior diagnosed or treated PCa. Any unrelated illness (e.g. active infection, inflammation or laboratory abnormalities) that in the judgment of the investigator will significantly affect patient's clinical status and/or outcome of the study. Any known allergy for the upfront therapy. Any known allergy for LHRH agonist or antagonist.

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PSMA response evaluation arm<br>PSMA-PET/CT response evaluation, 2 months after starting hormonal therapy, 2 months after starting upfront enzalutamide therapy | Diagnostic Test: PSMA-PET/CT response evaluation<br>* PSMA-PET/CT response evaluation, 2 months after starting hormonal therapy, 2 months after starting upfront enzalutamide therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRPC | Development of castration-resistant prostate cancer | 12-24 months after start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Second line therapy | Initiation of second line therapy | 12-24 months after start |