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PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)

Primary Purpose

Prostate Cancer, Prostate Cancer Metastatic, Metastatic Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
whole pelvic radiotherapy
metastasis-directed treatment
salvage Lymph Node Dissection
androgen deprivation therapy
Sponsored by
University Ghent
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Radiotherapy, metastasis-directed therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Epworth Healthcare
  • GZA
  • AZ St-Jan Brugge
  • AZ St-Lucas
  • Institut Jules Bordet
  • AZ Maria Middelares
  • University Hospital Ghent
  • AZ Groeninge
  • UZ Leuven
  • CH Mouscron
  • Humanitas Research Hospital
  • Vita-Salute San Raffaele University
  • Istituto Nazionale Tumori IRCCS
  • Fondazione IRCCS Policlinico S. Matteo
  • Ospedale Sacro Cuore-Don Calabria
  • Oslo University Hospital
  • Cruces University Hospital
  • Clínica Universitaria IMQ
  • Hospital Ramón y Cajal
  • Hospital Universitario La Princesa
  • Universitario Quironsalud
  • Hospitalario de Navarra
  • Hospital Clínico de Santiago
  • Hospital Universitari i Politècnic la Fe
  • Universitätsspital Basel
  • Universitätsklinik für Radio-Onkologie
  • Hôpitaux Universitaires de Genève
  • Kantonsspital St. Gallen
  • UniversitätsSpital Zürich

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

MDT + ADT

MDT + WPRT + ADT

Arm Description

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Toxicity: acute toxicity
Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.
Toxicity: late toxicity
Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.
Patient reported QOL as per EORTC-QLQ C30
Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients
Patient reported QOL as per EORTC-QLQ PR25
Validated questionnaire assessing the health-related QOL of prostate cancer patients
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
Overall survival
Overall survival will be read as the time from trial randomization to the date of death from any cause
Time to start of hormonal treatment
Time to hormonal treatment is defined as the time from trial randomization to start of hormonal treatment
Time to castration-resistant disease
Time to castration resistant disease is defined as the time from trial randomization until castration resistant status
economical evaluation
Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D-5L)
Sensitivity/specificity of PET-CT for the detection of nodal recurrences: limited to patients undergoing surgery
Sensitivity/specificity of PET-CT

Full Information

First Posted
June 14, 2018
Last Updated
June 27, 2023
Sponsor
University Ghent
Collaborators
University Hospital, Geneva
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1. Study Identification

Unique Protocol Identification Number
NCT03569241
Brief Title
PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases
Acronym
STORM
Official Title
PEACE V: A Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 27, 2018 (Actual)
Primary Completion Date
April 30, 2023 (Actual)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Ghent
Collaborators
University Hospital, Geneva

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Cancer Metastatic, Metastatic Cancer, Oligometastatic Cancer
Keywords
Radiotherapy, metastasis-directed therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
196 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MDT + ADT
Arm Type
Other
Arm Description
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy
Arm Title
MDT + WPRT + ADT
Arm Type
Experimental
Arm Description
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy
Intervention Type
Radiation
Intervention Name(s)
whole pelvic radiotherapy
Intervention Description
addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment
Intervention Type
Radiation
Intervention Name(s)
metastasis-directed treatment
Intervention Description
stereotactic body radiotherapy
Intervention Type
Procedure
Intervention Name(s)
salvage Lymph Node Dissection
Intervention Description
metastasis-directed treatment
Intervention Type
Drug
Intervention Name(s)
androgen deprivation therapy
Intervention Description
LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months
Primary Outcome Measure Information:
Title
Metastases-free survival
Description
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
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Clinical Progression free survival
Description
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
Time Frame
2 year
Title
Biochemical progression-free survival
Description
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
Time Frame
2 year
Title
Toxicity: acute toxicity
Description
Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.
Time Frame
3 months
Title
Toxicity: late toxicity
Description
Radiotherapy toxicity will be assessed according to NCI CTCAE v4.0.
Time Frame
2 year
Title
Patient reported QOL as per EORTC-QLQ C30
Description
Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients
Time Frame
2 year
Title
Patient reported QOL as per EORTC-QLQ PR25
Description
Validated questionnaire assessing the health-related QOL of prostate cancer patients
Time Frame
2 year
Title
Prostate cancer-specific survival
Description
Cancer specific survival will be read as the time from trial randomization to the date of death due to prostate cancer
Time Frame
5 year
Title
Overall survival
Description
Overall survival will be read as the time from trial randomization to the date of death from any cause
Time Frame
5 year
Title
Time to start of hormonal treatment
Description
Time to hormonal treatment is defined as the time from trial randomization to start of hormonal treatment
Time Frame
2 year
Title
Time to castration-resistant disease
Description
Time to castration resistant disease is defined as the time from trial randomization until castration resistant status
Time Frame
5 year
Title
economical evaluation
Description
Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D-5L)
Time Frame
2 year
Title
Sensitivity/specificity of PET-CT for the detection of nodal recurrences: limited to patients undergoing surgery
Description
Sensitivity/specificity of PET-CT
Time Frame
3 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Piet Ost, PhD
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
Epworth Healthcare
City
Melbourne
Country
Australia
Facility Name
GZA
City
Antwerp
Country
Belgium
Facility Name
AZ St-Jan Brugge
City
Brugge
Country
Belgium
Facility Name
AZ St-Lucas
City
Brugge
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussel
Country
Belgium
Facility Name
AZ Maria Middelares
City
Gent
Country
Belgium
Facility Name
University Hospital Ghent
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
CH Mouscron
City
Mouscron
Country
Belgium
Facility Name
Humanitas Research Hospital
City
Milan
Country
Italy
Facility Name
Vita-Salute San Raffaele University
City
Milan
Country
Italy
Facility Name
Istituto Nazionale Tumori IRCCS
City
Napoli
Country
Italy
Facility Name
Fondazione IRCCS Policlinico S. Matteo
City
Pavia
Country
Italy
Facility Name
Ospedale Sacro Cuore-Don Calabria
City
Verona
Country
Italy
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Cruces University Hospital
City
Barakaldo
Country
Spain
Facility Name
Clínica Universitaria IMQ
City
Bilbao
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Princesa
City
Madrid
Country
Spain
Facility Name
Universitario Quironsalud
City
Madrid
Country
Spain
Facility Name
Hospitalario de Navarra
City
Navarro
Country
Spain
Facility Name
Hospital Clínico de Santiago
City
Santiago
Country
Spain
Facility Name
Hospital Universitari i Politècnic la Fe
City
Valencia
Country
Spain
Facility Name
Universitätsspital Basel
City
Basel
Country
Switzerland
Facility Name
Universitätsklinik für Radio-Onkologie
City
Bern
Country
Switzerland
Facility Name
Hôpitaux Universitaires de Genève
City
Geneva
Country
Switzerland
Facility Name
Kantonsspital St. Gallen
City
Saint Gallen
Country
Switzerland
Facility Name
UniversitätsSpital Zürich
City
Zürich
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
35715340
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.
Results Reference
derived
PubMed Identifier
34961659
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.
Results Reference
derived
PubMed Identifier
33386290
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.
Results Reference
derived
PubMed Identifier
32398040
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.
Results Reference
derived

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PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

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