Clinical trial NCT03079323: Trial to Investigate the Benefit of Elective Para-Aortic Radiotherapy (PART) for pN1 Prostate Cancer
Official title: Phase II Trial to Investigate the Benefit of Elective Para-Aortic Radiotherapy (PART) for pN1 Prostate Cancer Using Arc Therapy (IMAT/VMAT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: External beam radiotherapy
Prostate cancer
Elective para-aortic radiation therapy
PART
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2017-03-14
Enrollment: 137
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical relapse-free survival (cRFS)
timeFrame: Median follow-up of 60 months
Secondary outcomes:
measure: Acute toxicity
timeFrame: Median follow-up of 90 days
measure: Late toxicity
timeFrame: Median follow-up of 3 years
measure: Quality-of-life - General
timeFrame: Median follow-up of 3 years
measure: Quality-of-life - Prostate specific
timeFrame: Median follow-up of 3 years
measure: Quality-of-life - Measure of health outcome
timeFrame: Median follow-up of 3 years
measure: Quality-of-life - Urinary incontinence
timeFrame: Median follow-up of 3 years
measure: Quality-of-life - Erectile function
timeFrame: Median follow-up of 3 years
measure: Time to palliative ADT
timeFrame: Median follow-up of 5 years
measure: Time to castration-refractory prostate cancer (CRPC)
timeFrame: Median follow-up of 5 years
measure: Cause-specific survival
timeFrame: Median follow-up of 5 years
measure: Overall survival
timeFrame: Median follow-up of 5 years
measure: In field pelvic disease control (at biological imaging)
timeFrame: Median follow-up of 5 years
measure: In field PA disease control (at biological imaging)
timeFrame: Median follow-up of 5 years
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: UZ Leuven
name: Gert De Meerleer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Draulans C, Joniau S, Fonteyne V, Delrue L, Decaestecker K, Everaerts W, Dirix P, Van den Bergh L, Crijns W, Vandendriessche H, Van Wynsberge L, Ost P, Lumen N, Buelens P, Haustermans K, Berghen C, De Meerleer G. Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial. JMIR Res Protoc. 2018 Dec 13;7(12):e11256. doi: 10.2196/11256.