Clinical trial NCT03876912: The Effect of ADT on PSMA Expression in Metastatic Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostate Specific Membrane Antigen
GnRH antagonist
Positron Emission Tomography
PSMA-PET/CT
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2019-03-15
Enrollment: 35
Sex: MALE
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: PSMA-flare after ADT
timeFrame: 2-3 weeks
Secondary outcomes:
measure: PSMA-flare in the follow-up until CRPC
timeFrame: 2-3 years
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Turku University Hospital
name: Jukka Kemppainen, Adj.Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Malaspina S, Ettala O, Tolvanen T, Rajander J, Eskola O, Bostrom PJ, Kemppainen J. Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naive metastatic prostate cancer patients. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):613-621. doi: 10.1007/s00259-022-05970-y. Epub 2022 Sep 26.