APalutamiAPalutamide and stEReotactic Body Radiation Therapy for Metastatic Prostate Cancer

Study Overview
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Brief Summary
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Final results from TITAN trial showed that apalutamide plus ADT improved OS in a population of patients with metastatic hormone sensitive prostate cancer (mHSPC), if compared to ADT alone. However, stereotactic body radiotherapy (SBRT) showed to improve outcomes of oligometastatic patients if compared to systemic therapy alone within modern randomized trial, including a mixed cohort of different pathologies. However, there are no trials specifically exploring the benefit offered by SBRT in oligometastatic mHSPC treated with Apalutamide if compared to Apalutamide alone associated to Androgen deprivation therapy. Thus, a randomized trial was designed to test specifically the hypotesis that SBRT will improve outcome in a selected population of oligometastatic mHSPC treated with Apalutamide and ADT, undergoing baseline staging according to local reimbursability.

Detailed Description
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Prospective Phase II randomized superiority study, open label, multicentric. Patients with Oligometastatic hormone sensitive prostate cancer defined as presence of ≤ 5 non-visceral metastatic lesions and treated with androgen deprivation treatment associated with Apalutamide will be randomized to receive standard systemic treatment alone or concomitant SBRT on all sites of metastatic disease.

Official Title
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APalutamide and stEReotactic Body Radiation Therapy for Low Burden Metastatic Hormone senSItive Prostate Cancer, a rANdomized Trial - PERSIAN

Conditions
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Oligometastatic Hormone Sensitive Prostate Cancer

Intervention / Treatment
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* Combination Product: SBRT on all sites of metastatic disease+Apalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have signed written informed consent Adult patients ≥ 18 years Oligometastatic hormone sensitive prostate cancer defined as presence of ≤ 5 non-visceral metastatic lesions *, ** All lesions must be amenable to SBRT in judgment of treating radiation oncologist *** Patients with metastatic recurrence after previous radical prostatectomy or definitive radiotherapy will be included in the trial, provided that radical approach on prostate is administered Androgen deprivation therapy (ADT) started ≤ 6 months before enrollment Patients should be eligible to Apalutamide treatment Exclusion Criteria: Presence of visceral disease De novo metastatic disease Any contraindication to the use of Apalutamide Any condition for which, in the opinion of the treating physician, SBRT should not be proposed or could be contraindicated

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized between control arm (Androgen Deprivation therapy and Apalutamide) or treatment arm (Androgen Deprivation therapy and Apalutamide and SBRT on all sites of metastatic disease)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Androgen Deprivation therapy and Apalutamide | Combination Product: SBRT on all sites of metastatic disease+Apalutamide<br>* oral Apalutamide 240 mg daily+ stereotactic body radiotherapy on all metastatic sites of disease, administered in 1-8 fractions for a total EQD2 of 50 Gy with an alpha/beta of 10.<br>|
| Experimental: Treatment<br>Androgen Deprivation therapy and Apalutamide and SBRT on all sites of metastatic disease | Combination Product: SBRT on all sites of metastatic disease+Apalutamide<br>* oral Apalutamide 240 mg daily+ stereotactic body radiotherapy on all metastatic sites of disease, administered in 1-8 fractions for a total EQD2 of 50 Gy with an alpha/beta of 10.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete biochemical response | Rate of patients with complete biochemical response (PSA < 0.2 ng/ml) | 6 months after treatment start. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from biochemical progression | Biochemical progression defined according to Prostate Cancer Working Group Criteria | 2 years after treatment | 
| Freedom from radiological progression | radiological progression defined according to Prostate Cancer Working Group Criteria | 2 years after treatment | 
| Rate of adverse events | measured according to Common Terminology Criteria for Adverse Events | 2 years after treatment | 
| Overall Survival | Time between randomization and death from any cause | 2 years after treatment | 
| Cancer Specific Survival | Time between randomization and death from prostate cancer | 2 years after treatment | 
| Health related quality of life | Measured with European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. | 2 years after treatment | 
| Health related quality of life | Measured with EORTC QLQ-PR25 questionnaire | 2 years after treatment |