Clinical trial NCT05539300: PSMA Response in Metastasized Hormone Sensitive Prostate Cancer - Enzalutamide
Official title: Individualisation of Management With Novel Upfront Therapies in Newly Diagnosed Metastasized Prostate Cancer Using (PSMA)PET/CT Imaging - Enzalutamide
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2022-09-14
Enrollment: 150
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: CRPC
timeFrame: 12-24 months after start
Secondary outcomes:
measure: Second line therapy
timeFrame: 12-24 months after start
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: Roderick van den Bergh
Study officials:
References: