The Effect of ADT on PSMA Expression in Metastatic Prostate Cancer

Study Overview
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Brief Summary
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Thirty-five men with newly diagnosed, metastatic prostate cancer are scanned with 18F-PSMA 1007 PET/CT at baseline, 3 weeks after the initiation of GnRH-antagonist, at one year and at the time of castration resistant prostate cancer (CRPC). The aim of the study is to classify metastatic lesions into those with PSMA-flare and those without and determine their potential to progress during the follow-up until CRPC.

Detailed Description
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In metastatic prostate cancer androgen deprivation therapy (ADT) has been traditionally used as a first line approach. Based on histological studies, animal models and PSMA-PET imaging, it is known that administration of ADT increases prostate specific membrane antigen (PSMA) expression. Preliminary results of our previous prospective clinical trial (clinicaltrials.gov identifier: NCT03313726) with nine men demonstrated a heterogenous flare in PSMA expression 2-3 weeks after ADT, more evidently in bone metastases. Our hypothesis is that metastatic lesions having PSMA-flare respond differently to ADT and have different outcome than those without PSMA-flare. Therefore, the objective of the study is to demonstrate the PSMA-flare seen in bone lesions 3 weeks after ADT and then determine the potential predictive value of the phenomenon in the progression to castration resistant prostate cancer (CRPC). Thirty-five men with newly diagnosed, metastatic PC will undergo 18F-PSMA 1007 PET/CT before and 3 weeks after the initiation of sub-cutaneous injection of GnRH-antagonist (Degarelix, Firmagon®). A subgroup of 20 patients will receive an additional FDG PET/CT scan before ADT to investigate whether lesions with PSMA flare show a different metabolic behaviour on FDG PET. During the follow-up, 18F-PSMA 1007 PET/CT will be also performed once a year. Finally all patients will repeat 18F-PSMA 1007 PET/CT at the time of CRPC. In addition to imaging, PSA is measured, and blood drawn for androgen levels and biomarkers in three months interval.

Official Title
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The Effect of Androgen Deprivation Therapy on the Expression of Prostate Specific Membrane Antigen (PSMA) Evaluated With 18F-PSMA PET/CT in Treatment naïve Metastatic Prostate Cancer Patients

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: GnRH antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 40 to 85 years old Language spoken: Finnish Diagnosis: Histologically confirmed adenocarcinoma of prostate Adequate histological sampling consisting of at least 3 biopsy samples from each lobe No previous surgical, radiation or endocrine treatment for prostate carcinoma Clinical stage:T1c-T4NanyM1 Serum creatinine ≤ 1,5 x ULN Mental status: Patients must be able to understand the meaning of the study Informed consent: The patient must sign the appropriate Ethical Committee approved informed consent documents in the presence of the designated staff Exclusion Criteria: Previous PC treatment Uncontrolled serious infection Prior usage of 5-ARI medication in past 12 months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: GnRH antagonist<br>Administration of GnRH antagonist (subcutaneous injection, 240 mg) after baseline 18F-PSMA 1007 PET/CT.Then 18F-PSMA 1007 PET/CT is repeated 3 weeks after ADT and at development of CRPC | Drug: GnRH antagonist<br>* 18F-PSMA 1007 PET/CT before, 3 weeks after ADT, at 1 year and at CRPC in 35 patients. 18F-FDG PET/CT in a subgroup of 20 patients before ADT.<br>* Other names: Degarelix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSMA-flare after ADT | Comparison of mean increase of SUVmax in 18F-PSMA 1007 PET between bone lesions and prostatic lesions after the initiation of ADT | 2-3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSMA-flare in the follow-up until CRPC | Compare SUVmax of lesions with PSMA flare and those without during the follow-up and at CRPC | 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Specific Membrane Antigen, GnRH antagonist, Positron Emission Tomography, PSMA-PET/CT