Immediate Curative vs Conservative Treatment in Older Men With M0, High-risk Prostate Cancer

Официальное название

A Randomized, Open-label, Multicenter, Parallel Group Treatment, Phase 3, Two-arm Study to Measure the Effect on Overall Survival and Quality of Life of Immediate Curative Therapy Compared With Standard Conservative Treatment in Older Male Participants Aged ≥ 75 Years With Non-metastatic, High-risk Prostate Cancer

Обзор

It is currently unclear if immediate curative treatment (radiotherapy or surgery) of high-risk prostate cancer without metastasis in older men (\>=75 years) generates the same survival benefits as in younger patients or if the harms/ side-effects of immediate curative treatment outweigh the benefits. In this study the investigators randomize older patients with high-risk, non-metastatic high-risk prostate cancer to either immediate curative therapy or to conservative, more problem-oriented therapy to investigate if immediate curative treatment prolongs life, improves quality of life and is cost-effective.

Подробное описание

There is a lack of both level 1 evidence and consensus regarding the optimal treatment strategy for older men (\>=75 years) with non-metastatic, high-risk prostate cancer. Currently, in Scandinavia, the majority of older patients are treated conservatively, i.e. with hormone therapy or watchful waiting while some centers recommend immediate curative therapy regardless of patient age. Older patients thus risk both undertreatment and overtreatment of their cancer. This randomized clinical trial investigates if immediate curative therapy of high-risk, non-metastatic prostate cancer prolongs life (as it does in younger patients) and improves health-related quality of life. Furthermore, this trial investigates if the early side effects of immediate curative therapy are compensated by better long-term tumor control, better quality of life, functional status and improved survival.

Вмешательства

• Лучевая терапия Radiotherapy or surgery
  see arm/ group description
• Другое initial observation
  see arm/ group description
• Препарат Hormone therapy
  androgen depression therapy (ADT) by either LHRH agonist or antagonist or androgen monotherapy

Первичные конечные точки

• Overall survival [Срок оценки: 10 years following end of recruitment]
• Burden of disease [Срок оценки: 0-10 years]

Вторичные конечные точки (9)

• Role functioning [Срок оценки: 0-10 years]
• Urinary irritative/ obstructive symptoms [Срок оценки: 0-10 years]
• bowel symptoms [Срок оценки: 0-10 years]
• Prostate cancer morbidity [Срок оценки: 0-10 years]
• Prostate-cancer-specific survival [Срок оценки: 0-10 years]
• Metastasis-free survival [Срок оценки: 0-10 years]
• Symptom-/ intervention-free survival [Срок оценки: 0-10 years]
• Quality of life-adjusted years [Срок оценки: 0-10 years]
• need for secondary and tertiary therapy [Срок оценки: 0-10 years]

Критерии участия

Критерии включения

• Participant must be 75 years of age or older, at the time of signing the informed consent.
• Participants who are healthy as determined by medical evaluation and geriatric G8/ miniCOGTM evaluation (G8: Fit, score >14, or reversibly frail; miniCOGTM: score >2)

And who have PCa (diagnosed ≤6 months) with one or both of the following features:

• Gleason grade 8-10 (ISUP group 4 and 5) other than microscopic, low-volume disease (tumor must be either palpable or visible on MRI, i.e., PIRADS 4 or 5)
• Locally advanced PCa (T3 or T4) (unequivocal findings of clinical/ radiological T3 or clinical/ radiological T4 on DRE or MRI; broad capsular contact of tumor on MRI is treated as localized disease, T2, in the context of this study)
• Able to read, understand and fill in HRQoL questionnaires (PROMS)
• Male
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Критерии исключения

Medical Conditions

• Dementia (unable to consent) Prior/Concomitant Therapy
• Prior radiation to the pelvis
• Hormone therapy >3 months prior to randomization Diagnostic assessments
• Lymph node metastasis (N0) on MRI, CT or PSMA-PET CT (equivocal N-findings =N0; borderline cases will be discussed and called by a study tumor board).
• Distant metastasis (M0) on MRI, CT, bone scan or PSMA-PET CT (equivocal bone scan findings need to be confirmed with MRI or CT; borderline cases will be discussed by a study tumor board).

Other Exclusions

• Disabled or severe comorbidity (identified by G8 screening)
• Unable to read, understand or fill out HRQoL questionnaires (PROMS)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Норвегия · 11 центров

• Sunmøre Hospital Trust — Ålesund
• Oslo University Hospital — Oslo
• Stavanger University Hospital — Stavanger
• Sørlandet Hospital Trust — Kristiansand
• Telemark Hospital Trust — Skien
• St. Olavs Hospital — Trondheim
• Vestfold Hospital Trust (Hospital of Vestfold) — Tønsberg
• Vestre Viken Hospital Trust — Drammen
• … и ещё 3 центра

Дания · 3 центра

• Rigshospital — Copenhagen
• Esbjerg and Grindsted Hospital — Esbjerg
• Odense University Hospital — Odense

Финляндия · 3 центра

• Helsinki University Hospital — Helsinki
• Tampere University Hospital — Tampere
• Turku University Hospital — Turku

Швеция · 1 центр

• Capio Saint Göran's Hospital — Stockholm

Публикации

• Loffeler S, Bertilsson H, Muller C, Aas K, Haugnes HS, Aksnessaether B, Pesonen M, Thon K, Tandstad T, Murtola T, Poulsen MH, Nordstrom T, Vigmostad MN, Ottosson F, Holmsten K, Christiansen O, Slaaen M, Haug ES, Storas AH, Asphaug L, Rannikko A, Brasso K; Scandinavian Prostate Cancer Group (SPCG) and the Norwegian Get-Randomized (GRand) Initiative. Protocol of a randomised, controlled trial compar PMID 38469686

Идентификаторы

NCT: NCT05448547 · GrandP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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