Trial to Investigate the Benefit of Elective Para-Aortic Radiotherapy (PART) for pN1 Prostate Cancer

Study Overview
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Brief Summary
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Prospective non-randomized phase 2 trial to study the efficacy of additional elective para-aortic RT (PART) in pN1 patients compared to those who were historically treated with adjuvant whole pelvic radiotherapy (WPRT) alone.

Detailed Description
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Rationale: In prostate cancer with histopathologically proven pelvic lymph node metastasis (pN1) after extended pelvic lymph node dissection, multimodality treatment consisting of treatment of the primary tumor, androgen deprivation therapy and whole pelvic radiotherapy offers the best results and is the standard-of-care. However, in case >1 pelvic lymph node is invaded by tumor, after extended pelvic lymph node dissection, 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic lymph nodes (M1a disease) in 25% of the cases as we observed in series. Therefore Elective Para-Aortic Radiotherapy (PART) may improve disease control. Objective: The main goal of this phase II study is to investigate whether elective para-aortic radiotherapy increases the clinical relapse-free survival (cRFS) defined as the absence of clinical relapse (cR) at biological imaging at 5 years. The secondary objectives of this study are: acute toxicity, late toxicity, quality of life (QoL), time to palliative androgen deprivation therapy (ADT), time to castration refractory prostate cancer (CRPC), cause-specific survival and in field pelvic and para-aortic disease control. Study design: The PART-trial is a non-randomized phase II trial. Study population: Men with histological proven adenocarcinoma of the prostate (cT1-4; pT2-4) and presence of pN1 disease after ePLND are eligible for the study. For trial-inclusion, pN1 disease is defined on the basis of one of following criteria: (1) two or more positive LN; (2) ratio positive LN / removed LN > 7%; (3) presence of extracapsular LN extension. Patients referred for external beam radiotherapy (EBRT) who fulfill the inclusion criteria and without any of the exclusion criteria will be included in the present trial after written informed consent. Intervention: Patients included in the PART-trial receive radiotherapy to the prostate or prostate bed and the pelvic lymph nodes according to the current standard. Furthermore patients in the PART-trial receive an additional elective radiation to the para-aortic lymph nodes. The total radiation dose that will be delivered to the para-aortic lymph node area is 45 Gy in 25 fractions of 1.8 Gy. Androgen deprivation therapy is foreseen in this trial for 24 months (long term). Main study parameters/endpoints: The primary endpoint is to evaluate whether the addition of an elective para-aortic irradiation for pN1 prostate cancer patients increases the clinical relapse-free survival (cRFS) defined as the absence of clinical relapse (cR) at biological imaging at 5 years. Clinical relapse-free survival is defined by a combination of PSA measurements and imaging. Secondary endpoints are acute and late gastrointestinal (GI) and genitourinary (GU) toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, QoL, time to palliative ADT, time to CRPC, cause-specific survival and in field pelvic and para-aortic disease control.

Official Title
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Phase II Trial to Investigate the Benefit of Elective Para-Aortic Radiotherapy (PART) for pN1 Prostate Cancer Using Arc Therapy (IMAT/VMAT)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: PART-trial


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent and willingness to comply with the treatment and follow-up Diagnosis of histopathologically confirmed prostate cancer No former treatment for prostate cancer Presence of pN1 disease after ePLND (criteria defined in the protocol) Age > 18 Karnofsky Performance score > 70 Ability to understand the informed consent (Helsinki Declaration) Exclusion Criteria: Recurrent disease status Presence of cM1a, cM1b or cM1c disease Former radiotherapy making WPRT and/or PART impossible Prior malignancy, not disease-free > 5 years, except basocellular skin epithelioma Severe or active comorbidity likely to impact on the feasibility of WPRT and/or PART Disorder precluding understanding of trial information

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PART-trial<br>External beam radiotherapy | Radiation: PART-trial<br>* Elective radiation to the para-aortic lymph nodes 45 Gy / 1.8 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical relapse-free survival (cRFS) | The absence of clinical relapse (cR) at biological imaging | Median follow-up of 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity | (CTCAE 4.0) | Median follow-up of 90 days | 
| Late toxicity | (CTCAE 4.0) | Median follow-up of 3 years | 
| Quality-of-life - General | EORTC QLQ-C30 | Median follow-up of 3 years | 
| Quality-of-life - Prostate specific | EORTC QLQ-PR25 | Median follow-up of 3 years | 
| Quality-of-life - Measure of health outcome | EQ-5D-5L | Median follow-up of 3 years | 
| Quality-of-life - Urinary incontinence | ICIQ-SF | Median follow-up of 3 years | 
| Quality-of-life - Erectile function | IIEF-5 | Median follow-up of 3 years | 
| Time to palliative ADT | Indications for palliative ADT or based on the EAU guidelines | Median follow-up of 5 years | 
| Time to castration-refractory prostate cancer (CRPC) | Criteria for CRPC as defined in the EAU guidelines | Median follow-up of 5 years | 
| Cause-specific survival | Cause-specific survival | Median follow-up of 5 years | 
| Overall survival | Overall survival | Median follow-up of 5 years | 
| In field pelvic disease control (at biological imaging) | In field pelvic disease control (PET-CT imaging (PSMA/choline) is performed in case of PSA progression) | Median follow-up of 5 years | 
| In field PA disease control (at biological imaging) | In field PA disease control (PET-CT imaging (PSMA/choline) is performed in case of PSA progression) | Median follow-up of 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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External beam radiotherapy, Prostate cancer, Elective para-aortic radiation therapy, PART