Clinical trial NCT05448547: Immediate Curative Vs Conservative Treatment in Older Men with M0, High-risk Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: prostate cancer
older patients
immediate curative treatment
conservative treatment
Lead sponsor: The Hospital of Vestfold
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: Klinbeforsk
First posted: 2022-07-07
Enrollment: 980
Sex: MALE
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, parallel, open-label
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Participant must be 75 years of age or older, at the time of signing the informed consent.
2. 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)
3. Male
4. 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.

Exclusion Criteria:

Medical Conditions

1. Dementia (unable to consent) Prior/Concomitant Therapy
2. Prior radiation to the pelvis
3. Hormone therapy \>3 months prior to randomization Diagnostic assessments
4. 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).
5. 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
6. Disabled or severe comorbidity (identified by G8 screening)
7. Unable to read, understand or fill out HRQoL questionnaires (PROMS)

Primary outcomes:
measure: Overall survival
timeFrame: 10 years following end of recruitment
measure: Burden of disease
timeFrame: 0-10 years
Secondary outcomes:
measure: Role functioning
timeFrame: 0-10 years
measure: Urinary irritative/ obstructive symptoms
timeFrame: 0-10 years
measure: bowel symptoms
timeFrame: 0-10 years
measure: Prostate cancer morbidity
timeFrame: 0-10 years
measure: Prostate-cancer-specific survival
timeFrame: 0-10 years
measure: Metastasis-free survival
timeFrame: 0-10 years
measure: Symptom-/ intervention-free survival
timeFrame: 0-10 years
measure: Quality of life-adjusted years
timeFrame: 0-10 years
measure: need for secondary and tertiary therapy
timeFrame: 0-10 years
Other outcomes:
measure: Institutionalized care
timeFrame: 0-10 years
measure: Health-related quality of life in cancer patients
timeFrame: 0-10 years
measure: Health-related quality of life in older cancer patients
timeFrame: 0-10 years
measure: Quality of Life issues in patients with prostate cancer
timeFrame: 0-10 years
measure: Instrumental activities of daily living (iADL)
timeFrame: 0-10 years
measure: Personal activities of daily living (pADL)
timeFrame: 0-10 years
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Ålesund
country: Norway
facility: Sunmøre Hospital Trust
state: Møre og Romsdal
city: Stavanger
country: Norway
facility: Stavanger University Hospital
state: Rogaland
city: Kristiansand
country: Norway
facility: Sørlandet Hospital Trust
state: Sørlandet
city: Skien
country: Norway
facility: Telemark Hospital Trust
state: Telemark
city: Trondheim
country: Norway
facility: St. Olavs Hospital
state: Trøndelag
city: Tønsberg
country: Norway
facility: Vestfold Hospital Trust (Hospital of Vestfold)
state: Vestfold
city: Drammen
country: Norway
facility: Vestre Viken Hospital Trust
city: Hamar
country: Norway
facility: Innlandet Hospital Trust
city: Lørenskog
country: Norway
facility: Akerhus University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Tromsø
country: Norway
facility: University Hospital of Northern Norway
city: Stockholm
country: Sweden
facility: Capio Saint Göran&#39;s Hospital
Study officials:
affiliation: The Hospital of Vestfold
name: Sven Loffeler, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: