Clinical trial NCT03569241: PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases
Official title: PEACE V: a Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Prostate Cancer Metastatic
Metastatic Cancer
Oligometastatic Cancer
Keywords: Radiotherapy
metastasis-directed therapy
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
First posted: 2018-06-26
Enrollment: 196
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).

Detailed description: A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of metastases, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.

Eligibility criteria: Inclusion Criteria:

* Histologically proven initial diagnosis of adenocarcinoma of the prostate
* Biochemical relapse of prostate cancer following radical local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2016.
* Following radical prostatectomy, patients with a biochemical relapse are eligible in case a nodal relapse is detected in the pelvis even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage).
* In case of a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence and patients with a confirmed local recurrence are eligible in case they also undergo a local salvage therapy. If imaging rules out local relapse, patients are eligible.
* Nodal relapse in the pelvis on choline, PSMA or FACBC PET-CT with a maximum of 3 positive nodal lymph nodes. The upper limit of the pelvis is defined as the aortic bifurcation.
* WHO performance state 0-1
* Age \>18 years
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

* Bone or visceral metastases
* Para-aortic lymph node metastases (above the aortic bifurcation)
* Local relapse in the prostate gland or prostate bed not suitable for a curative treatment
* Previous irradiation of the pelvic and or para-aortic nodes
* Serum testosterone level \<50ng/dl or 1.7 nmol/L at time of randomization
* Symptomatic metastases
* Lymph node metastases in previously irradiated areas resulting in dose constraint violation
* Contraindications to pelvic radiotherapy (chronic pelvic inflammatory bowel disease)
* Contraindications to androgen deprivation therapy
* PSA rise while on active treatment with (LHRH-agonist, LHRH-antagonist, anti-androgen, estrogen
* Previous treatment with cytotoxic agent for PCa
* Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,...)
* Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years before randomization.

Primary outcomes:
measure: Metastases-free survival
timeFrame: 2 year
Secondary outcomes:
measure: Clinical Progression free survival
timeFrame: 2 year
measure: Biochemical progression-free survival
timeFrame: 2 year
measure: Toxicity: acute toxicity
timeFrame: 3 months
measure: Toxicity: late toxicity
timeFrame: 2 year
measure: Patient reported QOL as per EORTC-QLQ C30
timeFrame: 2 year
measure: Patient reported QOL as per EORTC-QLQ PR25
timeFrame: 2 year
measure: Prostate cancer-specific survival
timeFrame: 5 year
measure: Overall survival
timeFrame: 5 year
measure: Time to start of hormonal treatment
timeFrame: 2 year
measure: Time to castration-resistant disease
timeFrame: 5 year
measure: economical evaluation
timeFrame: 2 year
measure: Sensitivity/specificity of PET-CT for the detection of nodal recurrences: limited to patients undergoing surgery
timeFrame: 3 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Epworth Healthcare
city: Antwerp
country: Belgium
facility: GZA
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge
city: Brugge
country: Belgium
facility: AZ St-Lucas
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mouscron
country: Belgium
facility: CH Mouscron
city: Milan
country: Italy
facility: Humanitas Research Hospital
city: Milan
country: Italy
facility: Vita-Salute San Raffaele University
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Verona
country: Italy
facility: Ospedale Sacro Cuore-Don Calabria
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barakaldo
country: Spain
facility: Cruces University Hospital
city: Bilbao
country: Spain
facility: Clínica Universitaria IMQ
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Universitario Quironsalud
city: Navarro
country: Spain
facility: Hospitalario de Navarra
city: Santiago
country: Spain
facility: Hospital Clínico de Santiago
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic la Fe
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Universitätsklinik für Radio-Onkologie
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
Study officials:
affiliation: University Hospital, Ghent
name: Piet Ost, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huck C, Achard V, Zilli T. Surgical Treatments of Benign Prostatic Hyperplasia and Prostate Cancer Stereotactic Radiotherapy: Impact on Long-Term Genitourinary Toxicity. Clin Oncol (R Coll Radiol). 2022 Sep;34(9):e392-e399. doi: 10.1016/j.clon.2022.05.021. Epub 2022 Jun 15.
citation: Corkum MT, Achard V, Morton G, Zilli T. Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go? Clin Oncol (R Coll Radiol). 2022 May;34(5):340-349. doi: 10.1016/j.clon.2021.12.006. Epub 2021 Dec 25.
citation: Zilli T, Dirix P, Heikkila R, Liefhooghe N, Siva S, Gomez-Iturriaga A, Everaerts W, Otte F, Shelan M, Mercier C, Achard V, Thon K, Stellamans K, Moon D, Conde-Moreno A, Papachristofilou A, Scorsetti M, Guckenberger M, Ameye F, Zapatero A, Van De Voorde L, Lopez Campos F, Counago F, Jaccard M, Spiessens A, Semac I, Vanhoutte F, Goetghebeur E, Reynders D, Ost P. The Multicenter, Randomized, Phase 2 PEACE V-STORM Trial: Defining the Best Salvage Treatment for Oligorecurrent Nodal Prostate Cancer Metastases. Eur Urol Focus. 2021 Mar;7(2):241-244. doi: 10.1016/j.euf.2020.12.010. Epub 2020 Dec 29.
citation: De Bruycker A, Spiessens A, Dirix P, Koutsouvelis N, Semac I, Liefhooghe N, Gomez-Iturriaga A, Everaerts W, Otte F, Papachristofilou A, Scorsetti M, Shelan M, Siva S, Ameye F, Guckenberger M, Heikkila R, Putora PM, Zapatero A, Conde-Moreno A, Counago F, Vanhoutte F, Goetghebeur E, Reynders D, Zilli T, Ost P. PEACE V - Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial. BMC Cancer. 2020 May 12;20(1):406. doi: 10.1186/s12885-020-06911-4.