PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

Prostate Cancer Clinical Trial

— STORM  

Official title:

PEACE V: A Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03569241
• Other study ID #: EC/2018/0130
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 27, 2018
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2023
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 196
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Oligometastatic Cancer
• Prostate Cancer
• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Radiation:
• whole pelvic radiotherapy
addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment
• metastasis-directed treatment
stereotactic body radiotherapy

Procedure:
• salvage Lymph Node Dissection
metastasis-directed treatment

Drug:
• androgen deprivation therapy
LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

Locations

Country	Name	City	State
Australia	Epworth Healthcare	Melbourne
Belgium	GZA	Antwerp
Belgium	AZ St-Jan Brugge	Brugge
Belgium	AZ St-Lucas	Brugge
Belgium	Institut Jules Bordet	Brussel
Belgium	AZ Maria Middelares	Gent
Belgium	University Hospital Ghent	Ghent
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CH Mouscron	Mouscron
Italy	Humanitas Research Hospital	Milan
Italy	Vita-Salute San Raffaele University	Milan
Italy	Istituto Nazionale Tumori IRCCS	Napoli
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	Ospedale Sacro Cuore-Don Calabria	Verona
Norway	Oslo University Hospital	Oslo
Spain	Cruces University Hospital	Barakaldo
Spain	Clínica Universitaria IMQ	Bilbao
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Universitario Quironsalud	Madrid
Spain	Hospitalario de Navarra	Navarro
Spain	Hospital Clínico de Santiago	Santiago
Spain	Hospital Universitari i Politècnic la Fe	Valencia
Switzerland	Universitätsspital Basel	Basel
Switzerland	Universitätsklinik für Radio-Onkologie	Bern
Switzerland	Hôpitaux Universitaires de Genève	Geneva
Switzerland	Kantonsspital St. Gallen	Saint Gallen
Switzerland	UniversitätsSpital Zürich	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
University Ghent	University Hospital, Geneva

Countries where clinical trial is conducted

Australia,  Belgium,  Italy,  Norway,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastases-free survival	Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by choline, FACBC or PSMA PET-CT or death due to any cause	2 year
Secondary	Clinical Progression free survival	Clinical Progression-free survival is defined as time between randomization and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause	2 year
Secondary	Biochemical progression-free survival	For patients who had previous RP at initial diagnosis, a biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/ml with a confirmatory rise at least 2 weeks later. For patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA	2 year
Secondary	Toxicity: acute toxicity	Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.	3 months
Secondary	Toxicity: late toxicity	Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.	2 year
Secondary	Patient reported QOL as per EORTC-QLQ C30	Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients	2 year
Secondary	Patient reported QOL as per EORTC-QLQ PR25	Validated questionnaire assessing the health-related QOL of prostate cancer patients	2 year
Secondary	Prostate cancer-specific survival	Cancer specific survival will be read as the time from trial randomization to the date of death due to prostate cancer	5 year
Secondary	Overall survival	Overall survival will be read as the time from trial randomization to the date of death from any cause	5 year
Secondary	Time to start of hormonal treatment	Time to hormonal treatment is defined as the time from trial randomization to start of hormonal treatment	2 year
Secondary	Time to castration-resistant disease	Time to castration resistant disease is defined as the time from trial randomization until castration resistant status	5 year
Secondary	economical evaluation	Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D-5L)	2 year
Secondary	Sensitivity/specificity of PET-CT for the detection of nodal recurrences: limited to patients undergoing surgery	Sensitivity/specificity of PET-CT	3 months