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

Prostate Cancer Clinical Trial

— GrandP/SPCG19  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05448547
• Other study ID #: GrandP
• Status: Recruiting
• Phase: Phase 3
• Start date: November 4, 2022
• Est. completion date: December 31, 2036

Study information

• Verified date: September 2023
• Source: The Hospital of Vestfold
• Contact: Sven Loffeler, MD, PhD
• Phone: +47 92235628
• Email: sven.loffeler[@]siv.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 980
• Est. completion date: December 31, 2036
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 75 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• Radiotherapy or surgery
see arm/ group description

Other:
• initial observation
see arm/ group description

Drug:
• Hormone therapy
androgen depression therapy (ADT) by either LHRH agonist or antagonist or androgen monotherapy

Locations

Country	Name	City	State
Denmark	Rigshospital	Copenhagen
Denmark	Odense University Hospital	Odense
Finland	Tampere University Hospital	Tampere
Norway	Sunmøre Hospital Trust	Ålesund	Møre Og Romsdal
Norway	Innlandet Hospital Trust	Hamar
Norway	Sørlandet Hospital Trust	Kristiansand	Sørlandet
Norway	Akerhus University Hospital	Lørenskog
Norway	Oslo University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger	Rogaland
Norway	Vestfold Hospital Trust (Hospital of Vestfold)	Tønsberg	Vestfold
Norway	University Hospital of Northern Norway	Tromsø
Norway	St. Olavs Hospital	Trondheim	Trøndelag

Sponsors (3)

Lead Sponsor	Collaborator
Sven Löffeler	Klinbeforsk, Oslo University Hospital

Countries where clinical trial is conducted

Denmark,  Finland,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Institutionalized care	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.	0-10 years
Other	Health-related quality of life in cancer patients	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)	0-10 years
Other	Health-related quality of life in older cancer patients	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)	0-10 years
Other	Quality of Life issues in patients with prostate cancer	Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26), scales not secondary outcomes (score 0-100, higher scores indicating better outcomes)	0-10 years
Other	Instrumental activities of daily living (iADL)	Lawton and Brody questionnaire (8 questions, minimum score 0, maximum score 5, higher scores indicating need for assistance)	0-10 years
Other	Personal activities of daily living (pADL)	Lawton and Brody questionnaire (6 questions, minimum score 0, maximum score 5, higher scores indicating need for assistance)	0-10 years
Primary	Overall survival	overall survival	10 years following end of recruitment
Primary	Burden of disease	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)	0-10 years
Secondary	Role functioning	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)	0-10 years
Secondary	Urinary irritative/ obstructive symptoms	Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26),urinary scales (score 0-100, higher scores indicating better outcomes)	0-10 years
Secondary	bowel symptoms	Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26), bowel scales (score 0-100, higher scores indicating better outcomes)	0-10 years
Secondary	Prostate cancer morbidity	hospitalizations, interventions, complications due to local progression/ systemic progression)	0-10 years
Secondary	Prostate-cancer-specific survival	Prostate cancer deaths in intervention and control group	0-10 years
Secondary	Metastasis-free survival	time to metastasis detected radiographically due to symptoms or biochemical progression	0-10 years
Secondary	Symptom-/ intervention-free survival	time to symptoms/ need for interventions due to prostate cancer progression	0-10 years
Secondary	Quality of life-adjusted years	Euro QoL group questionaire (EQ-5D-5L) (1 =full health; 0= dead)	0-10 years
Secondary	need for secondary and tertiary therapy	use of second- and third-line therapies	0-10 years