GrandP/SPCG19: Immediate Curative vs Conservative Treatment in Older Men With M0, High-risk Prostate Cancer

Sponsor

Sven Löffeler (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05448547

Collaborator

Oslo University Hospital (Other), Klinbeforsk (Other)

980

Enrollment

Locations

Arms

171

Anticipated Duration (Months)

89.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: Radiotherapy or surgery Other: initial observation Drug: Hormone therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

980 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, parallel, open-labelrandomized, parallel, open-label

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2029

Anticipated Study Completion Date :

Dec 31, 2036

Arms and Interventions

Arm	Intervention/Treatment
Experimental: immediate curative therapy Patients randomized to the intervention arm will receive immediate curative therapy in the form of either radiotherapy to the prostate in combination with hormone therapy (ADT or monotherapy) or surgery (radical prostatectomy). Standard treatment in this arm is radiotherapy + hormone therapy. Surgery is reserved for patients with strong preferences against radiotherapy.	Radiation: Radiotherapy or surgery see arm/ group description
Active Comparator: initial observation/ hormone therapy Patients in this arm will either be observed (with localized high-risk prostate cancer) or receive hormone therapy (locally advanced prostate cancer; ADT or monotherapy). Further local or systemic therapy is given at doctor's discretion triggered by local or/ and systemic progression.	Other: initial observation see arm/ group description Drug: Hormone therapy androgen depression therapy (ADT) by either LHRH agonist or antagonist or androgen monotherapy

Arm

Intervention/Treatment

Experimental: immediate curative therapy

Patients randomized to the intervention arm will receive immediate curative therapy in the form of either radiotherapy to the prostate in combination with hormone therapy (ADT or monotherapy) or surgery (radical prostatectomy). Standard treatment in this arm is radiotherapy + hormone therapy. Surgery is reserved for patients with strong preferences against radiotherapy.

Radiation: Radiotherapy or surgery

see arm/ group description

Active Comparator: initial observation/ hormone therapy

Patients in this arm will either be observed (with localized high-risk prostate cancer) or receive hormone therapy (locally advanced prostate cancer; ADT or monotherapy). Further local or systemic therapy is given at doctor's discretion triggered by local or/ and systemic progression.

Other: initial observation

see arm/ group description

Drug: Hormone therapy

androgen depression therapy (ADT) by either LHRH agonist or antagonist or androgen monotherapy

Outcome Measures

Primary Outcome Measures

Overall survival [10 years following end of recruitment]
overall survival
Burden of disease [0-10 years]
European Organisation for Research and Treatment of Cancer questionnaire for assessment of health-related quality of life elderly patients with cancer (EORTC ELD 14), burden of disease scale (2 questions, score 0-100, high scores indicate high burden of disease)

Secondary Outcome Measures

Role functioning [0-10 years]
European Organisation for Research and Treatment of Cancer questionnaire for quality of life of cancer patients (EORTC-QLQ-C30), RF2 scale (2 questions, score 0-100, high scores indicate a high / healthy level of functioning)
Urinary irritative/ obstructive symptoms [0-10 years]
Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26),urinary scales (score 0-100, higher scores indicating better outcomes)
bowel symptoms [0-10 years]
Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26), bowel scales (score 0-100, higher scores indicating better outcomes)
Prostate cancer morbidity [0-10 years]
hospitalizations, interventions, complications due to local progression/ systemic progression)
Prostate-cancer-specific survival [0-10 years]
Prostate cancer deaths in intervention and control group
Metastasis-free survival [0-10 years]
time to metastasis detected radiographically due to symptoms or biochemical progression
Symptom-/ intervention-free survival [0-10 years]
time to symptoms/ need for interventions due to prostate cancer progression
Quality of life-adjusted years [0-10 years]
Euro QoL group questionaire (EQ-5D-5L) (1 =full health; 0= dead)
need for secondary and tertiary therapy [0-10 years]
use of second- and third-line therapies

Other Outcome Measures

Institutionalized care [0-10 years]
at each follow-up visit the living status of the patients will be assessed. If patients have become dependent on permanent nursing home/ assisted care this will be registered.
Health-related quality of life in cancer patients [0-10 years]
European Organisation for Research and Treatment of Cancer questionnaire for quality of life of cancer patients (EORTC-QLQ-C30), scales not primary/ secondary outcome measures (All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems)
Health-related quality of life in older cancer patients [0-10 years]
European Organisation for Research and Treatment of Cancer questionnaire for quality of life of cancer patients (EORTC-QLQ-C30), scales not primary outcome (All of the scales and single-item measures range in score from 0 to 100. High scores indicate poor mobility, good family support, much worry about the future, good maintenance of autonomy and purpose)
Quality of Life issues in patients with prostate cancer [0-10 years]
Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26), scales not secondary outcomes (score 0-100, higher scores indicating better outcomes)
Instrumental activities of daily living (iADL) [0-10 years]
Lawton and Brody questionnaire (8 questions, minimum score 0, maximum score 5, higher scores indicating need for assistance)
Personal activities of daily living (pADL) [0-10 years]
Lawton and Brody questionnaire (6 questions, minimum score 0, maximum score 5, higher scores indicating need for assistance)

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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.

Exclusion Criteria:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rigshospital	Copenhagen		Denmark
2	Odense University Hospital	Odense		Denmark
3	Tampere University Hospital	Tampere		Finland
4	Sunmøre Hospital Trust	Ålesund	Møre Og Romsdal	Norway
5	Stavanger University Hospital	Stavanger	Rogaland	Norway
6	Sørlandet Hospital Trust	Kristiansand	Sørlandet	Norway	4604
7	St. Olavs Hospital	Trondheim	Trøndelag	Norway	7006
8	Vestfold Hospital Trust (Hospital of Vestfold)	Tønsberg	Vestfold	Norway	3103
9	Innlandet Hospital Trust	Hamar		Norway
10	Oslo University Hospital	Oslo		Norway
11	University Hospital of Northern Norway	Tromsø		Norway