ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable)

May 10, 2023 updated by: UNICANCER

A Double-blind Randomised Phase III Trial Evaluating the Efficacy of ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability and Not Elected for Docetaxel or Androgen Receptor Targeted Agents

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors. The study plans to enroll 300 patients who will be randomized (1:1) to receive either: (i) Experimental arm: ADT + darolutamide 600 mg po bid, or (ii) Control arm: ADT + placebo po bid. Response to treatment will be assessed according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Scher, 2016). Treatment will be continued until radiographic disease progression. Treatment may also be terminated at the initiative of either the patient or the investigator for any reason that would be beneficial to the patient, including: unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient request. Following treatment discontinuation patients will enter the follow-up period and will be monitored for up to 10 years with regards to survival status, subsequent antineoplastic treatments and the status of ongoing adverse events (AEs) and/or new investigational product related AEs.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Charleroi, Belgium, 6000
        • Recruiting
        • Grand Hôpital de Charleroi - Site Notre Dame
        • Contact:
      • Haine-Saint-Paul, Belgium, 7100
        • Not yet recruiting
        • Groupe Jolimont - Hôpital de Jolimont
        • Contact:
      • Namur, Belgium, 5000
      • Ottignies, Belgium, 1340
        • Recruiting
        • Clinique Saint Pierre
        • Contact:
  • France
      • Avignon, France, 84918
        • Recruiting
        • Institut Sainte Catherine
        • Contact:
      • Bayonne, France, 64109
        • Recruiting
        • Centre Hospitalier Cote basque
        • Contact:
      • Besançon, France, 25000
        • Recruiting
        • CHU Besançon - Hopital Jean Mijoz
        • Contact:
      • Bordeaux, France, 22076
      • Brest, France, 29200
      • Caen, France, 14076
      • Chambéry, France, 73000
      • Clermont-Ferrand, France, 63011
      • Créteil, France, 94010
      • Dijon, France, 21079
        • Recruiting
        • Centre Georges Francois Leclerc
        • Contact:
      • Grenoble, France, 38043
        • Recruiting
        • CHU Grenoble
        • Contact:
      • La Roche-sur-Yon, France, 85925
      • Le Mans, France, 72000
        • Recruiting
        • CHU Le Mans
        • Contact:
      • Lille, France, 59000
        • Recruiting
        • Centre OSCAR LAMBRET
        • Contact:
      • Limoges, France, 87000
        • Recruiting
        • Polyclinique de Limoges
        • Contact:
      • Lorient, France, 56322
        • Recruiting
        • Groupe Hospitalier Bretagne Sud
        • Contact:
      • Lyon, France, 69373
      • Marseille, France, 13273
        • Recruiting
        • Institut Paoli-Calmettes
        • Contact:
      • Mougins, France, 06250
        • Not yet recruiting
        • Centre Azuréen de Cancérologie
        • Contact:
      • Nice, France, 06189
      • Nîmes, France, 30029
      • Paris, France, 75908
        • Recruiting
        • Hopital Europeen Georges Pompidou
        • Contact:
      • Paris, France, 75005
        • Not yet recruiting
        • Institut Curie
        • Contact:
          • Zahra Castel Ajgal, MD
        • Contact:
      • Paris, France, 75970
        • Not yet recruiting
        • Hopital Tenon
        • Contact:
      • Paris, France, 75475
        • Not yet recruiting
        • Hôpital Saint louis
        • Contact:
      • Paris, France, 75020
        • Recruiting
        • Centre Groupe Hospitalier Diaconesses Croix Saint-Simon
        • Contact:
      • Pierre-Bénite, France, 69310
        • Recruiting
        • Hospices Civils de Lyon -Lyon Sud
        • Contact:
      • Poitiers, France, 86021
        • Not yet recruiting
        • CHU de Poitiers - Pôle Régional de Cancérologie
        • Contact:
      • Pringy, France, 74374
      • Quimper, France, 29107
      • Reims, France, 51056
      • Rennes, France, 35042
      • Rodez, France, 12027
        • Recruiting
        • Centre Hospitalier Rodez
        • Contact:
      • Saint Grégoire, France, 35760
        • Recruiting
        • CHP Centre Saint Grégoire
        • Contact:
      • Saint Mandé, France, 94160
        • Recruiting
        • Hôpital Instruction des Armées - BEGIN
        • Contact:
      • Saint-Étienne, France, 42055
      • Saint-Étienne, France, 42100
      • Strasbourg, France, 67200
        • Recruiting
        • Institut de cancerologie Strasbourg Europe
        • Contact:
      • Strasbourg, France, 67000
        • Recruiting
        • Clinique Sainte Anne - Strasbourg Oncologie Libérale
        • Contact:
      • Suresnes, France, 92151
        • Recruiting
        • Hôpital FOCH
        • Contact:
      • Toulon, France, 83056
        • Recruiting
        • Centre Hospitalier Intercommunal de Toulon-La Seyne - Hôpital Ste Musse
        • Contact:
      • Toulouse, France, 31059
      • Toulouse, France, 31076
      • Tours, France, 37044
      • Vandœuvre-lès-Nancy, France, 54500
        • Recruiting
        • Institut de Cancérologie de Lorraine
        • Contact:
      • Villejuif, France, 94805
  • Ireland
      • Dublin, Ireland, D24 NR0A
      • Dublin, Ireland
        • Not yet recruiting
        • Mater Misericordiae University Hospital
        • Contact:
      • Dublin, Ireland, D04 T6F4
        • Recruiting
        • St Vincent's University Hospital
        • Contact:
      • Dublin, Ireland
        • Not yet recruiting
        • Mater Private Hospital
        • Contact:
  • Spain
      • Badalona, Spain
        • Not yet recruiting
        • Institut Catala d'Oncologia, Badalona-Hospital Germans Trias i Pujol
        • Contact:
      • Barcelona, Spain
      • Barcelona, Spain
      • Barcelona, Spain
        • Not yet recruiting
        • Vall d'Hebron Institute of Oncology. Vall d'Hebron University Hospital
        • Contact:
      • Girona, Spain
        • Not yet recruiting
        • Institut Catala d'Oncologia de Girona
        • Contact:
      • Madrid, Spain
        • Not yet recruiting
        • Hospital Universitario 12 de octubre
        • Contact:
      • Madrid, Spain
      • Manresa, Spain
        • Recruiting
        • Althaia, Xara Assistencial Universitaria Mansera
        • Contact:
      • Valencia, Spain
        • Recruiting
        • Fundacion Instituto Valenciano de Oncologia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed a written informed consent form prior to any trial specific procedures.
  2. Men with histologically or cytologically confirmed adenocarcinoma of the prostate.
  3. Aged ≥18 years old at the time of signing informed consent.

  4. De novo metastatic disease defined by clinical or radiological evidence of metastases.

    Note: For patients with nodal metastases only, only patients with extra-pelvic enlarged lymph nodes (lymph nodes located above the iliac bifurcation) can be included if they have either:

    • At least one extra-pelvic lymph node ≥2 cm
    • At least one extra-pelvic lymph node ≥1 cm if the patients also have at least one pelvic lymph node ≥2 cm
  5. Measurable disease or bone lesions that are evaluable according to PCWG3 criteria.

  6. Ineligible for treatment with all of the following drugs: docetaxel, abiraterone, enzalutamide, apalutamide; AND meets at least one of the following frailty criteria:

    1. Activities of daily living (ADL) assessment (excluding urinary incontinence question) score 3 or 4/5;
    2. 4-Instrumental activities of daily living (4-IADL) assessment score 2 or 3/4;
    3. A Grade 3 event on the Cumulative Illness Score Rating-Geriatrics (CISR-G) questionnaire;
    4. Body mass index (BMI) ≤21 kg/m² and/or >10% weight loss in the last 6 months;
    5. Timed up and go test (TUG) >14 sec.
  7. Adequate bone marrow function: haemoglobin ≥80 g/L, white blood cells ≥3.0 x10⁹/L and platelets ≥80 x10⁹/L.
  8. Adequate liver function: alanine aminotransferase (ALT) <2 x upper limit of normal (ULN) and bilirubin <1.5 x ULN, (or if bilirubin is between 1.5-2 x ULN, they must have a normal conjugated bilirubin). For patients with documented liver metastasis, ALT <5 x ULN is acceptable.
  9. Adequate renal function: calculated creatinine clearance >30 ml/min (using the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD EPI) method).
  10. For sexually active men, agreement to use adequate contraception for the duration of trial participation and up to 2 weeks after completing study treatment.
  11. Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
  12. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

  1. Three or more Grade 3, or any Grade 4 events on the CISR-G questionnaire.
  2. Eastern Cooperative Oncology Group (ECOG) performance status score ≥3.
  3. Hypertension not controlled by an anti-hypertensive treatment (systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥95 mmHg; 3 consecutive measures taken 5 minutes apart).
  4. Acute toxicities of prior treatments and procedures not resolved to grade ≤1 or baseline before randomisation, with the exception of hot flushes and erectile dysfunction.
  5. Previous systemic treatment for prostate cancer, except less than 12 weeks of ADT and/or an old-generation AR inhibitor.
  6. Severe or uncontrolled concurrent disease, infection or co-morbidity.
  7. Known hypersensitivity to the study treatment or any of its ingredients.
  8. Major surgery within 28 days before randomisation.
  9. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
  10. Prior malignancy ≤3 years before study enrolment. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any localized cancer for which treatment has been completed ≥6 months before randomisation and from which the subject has been disease-free, or for which the risk of relapse is less than 30%, as well as early stage chronic lymphocytic leukaemia that does not require any specific treatment.
  11. Inability to swallow oral medications.
  12. Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.
  13. Known to have active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease at screening.
  14. Treatment with any investigational product within 28 days before randomisation.
  15. Concurrent participation in another clinical trial involving an investigational product (patients enrolled in non-experimental trials with no modification of the standard of care can be included).
  16. Individual deprived of liberty or placed under the authority of a tutor.
  17. Significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition that, in the opinion of the investigator, would preclude participation in this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ADT + darolutamide
ADT + darolutamide 600 mg po bid
Drug: Darolutamide 300 mg
600 mg po, b.i.d.
Other Names:
  • Nubeqa®
Drug: Androgen deprivation therapy
Use according to local standard of care
Other Names:
  • ADT
Placebo Comparator: ADT + placebo
ADT + placebo po bid
Drug: Androgen deprivation therapy
Use according to local standard of care
Other Names:
  • ADT
Drug: Placebo
po, b.i.d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic progression-free survival
Time Frame: From randomisation to radiographic progression or death, up to 18 months
Time from randomisation to radiographic progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria or death, whichever occurs first
From randomisation to radiographic progression or death, up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Castration-resistant prostate cancer-free survival
Time Frame: From randomisation to onset of CRPC or death, up to 18 months
Time from randomisation to onset of castrate resistant prostate cancer (CRPC) according to PCWG3 criteria, or death, whichever occurs first
From randomisation to onset of CRPC or death, up to 18 months
Clinical progression-free survival
Time Frame: From randomisation to clinical progression or death, up to 18 months

Time from randomisation to first occurrence of any one of the following:

(i) Cancer pain deterioration (2-point deterioration from baseline according to the Brief Pain Inventory - Short Form [BPI-SF] questionnaire; initiation of opioid therapy, or a ≥30% increase in opiate use) (ii) Any deterioration of physical function measured using the 4-IADL assessment tools (Lawton, 1969) (iii) A deterioration in ECOG performance status of at least 2 points from baseline (iv) Death from any cause.
From randomisation to clinical progression or death, up to 18 months
Overall survival
Time Frame: From randomization to death from any cause, up to 10 years.
Time from randomisation to the time of death from any cause
From randomization to death from any cause, up to 10 years.
Frequency and severity of adverse events
Time Frame: From inclusion until 100 days after last dose of investigational product
The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders
From inclusion until 100 days after last dose of investigational product
Time to worsening in prostate cancer-related urinary symptoms
Time Frame: On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year

Time from randomisation to first increase from baseline of greater or equal to 8 points in the urinary symptom scale/score (PRURI) measured using the prostate cancer module of the EORTC quality of life questionnaire (EORTC-QLQ-PR25).

This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30. The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.
On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Time to next symptomatic skeletal event
Time Frame: From randomisation to occurence of a skeletal event, up to 18 months
Time from randomisation until first occurrence of one of the following: a symptomatic fracture, radiation or surgery to bone or a spinal cord compression
From randomisation to occurence of a skeletal event, up to 18 months
Complete prostate specific antigen (PSA) response
Time Frame: At 6 months
Defined according to PCWG3 criteria as PSA ≤ 0.2 ng/ml
At 6 months
Prostate cancer-specific survival
Time Frame: From randomization to death from prostate cancer, up to 10 years.
Time from randomisation to the date of death due to prostate cancer (deaths due to other causes will be censored)
From randomization to death from prostate cancer, up to 10 years.
Time to first subsequent systemic anti-cancer therapy (SACT)
Time Frame: From randomization up to 10 years.
Time from randomisation to the date of initiation of any SACT for CRPC, following initiation of the study treatment
From randomization up to 10 years.
Second line radiographic progression-free survival
Time Frame: From randomization up to 10 years.
Time from the date of initiation of a second SACT for CRPC to radiographic progression or death, whichever occurs first.
From randomization up to 10 years.
Second line overall survival
Time Frame: From randomization up to 10 years.
Time from the date of initiation of a second SACT for CRPC to death
From randomization up to 10 years.
Progression-free survival after next line of treatment (PFS2)
Time Frame: From randomization up to 10 years.
Time from randomisation to second objective disease progression, or death from any cause, whichever first
From randomization up to 10 years.
Geriatric status
Time Frame: At baseline and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year

Evaluated using the G-CODE (Paillaud, 2018), a core set of commonly used tools/items for geriatric assessment which has been validated for the collection of geriatric data in clinical cancer trials of older adults, enabling comparison across trials. The tools/items proposed in G-CODE are:

(i) Social assessment: living alone or support requested to stay at home; (ii) Functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire (4-IADL); (iii) Mobility: Timed Up and Go test; (iv) Nutrition: weight loss during the past 6 months and body mass index; (v) Cognition: Mini-Cog test; (vi) Mood: mini-Geriatric Depression Scale; (vii) Comorbidity: updated Charlson Comorbidity Index.
At baseline and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Time to deterioration for EORTC QLQ-PR25 symptom subscales
Time Frame: On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Defined as the first decline in the HRQoL score from baseline equal to or greater than the minimally important difference (MID; a measure of clinical significance) defined as half the standard deviation of the baseline value for each subscale. The prostate cancer module QLQ-PR25 is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.
On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Health related quality of life questionnaire EORTC-QLQ-C30
Time Frame: On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Health related quality of life questionnaire EORTC-QLQ-PR25
Time Frame: On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year

This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30.

The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.
On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
Health related quality of life questionnaire Brief Pain Inventory - Short Form (BPI-SF)
Time Frame: On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year
The Brief Pain Inventory is a self reporting tool to assess the severity of pain and the impact of pain on daily functions in patients with chronically painful diseases or conditions such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as postoperative pain. The Short Form of the questionnaire (BPI-SF) has been specifically developed for clinical trials.
On treatment day 1 and every 120 days during first years of treatment and every 180 days thereafter if treatment is continued for more than 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Collaborators

Bayer

Investigators

  • Principal Investigator: Giulia Baciarello, MD, San Camillo-Forlanino hospital, Italy
  • Principal Investigator: Karim Fizazi, MD, Gustave Roussy Cancer Campus, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2022

Primary Completion (Anticipated)

March 1, 2028

Study Completion (Anticipated)

September 1, 2033

Study Registration Dates

First Submitted

June 4, 2021

First Submitted That Met QC Criteria

June 4, 2021

First Posted (Actual)

June 7, 2021

Study Record Updates

Last Update Posted (Actual)

May 11, 2023

Last Update Submitted That Met QC Criteria

May 10, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-GTG-2006
  • 2020-003663-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD can be shared upon request to the sponsor

IPD Sharing Time Frame

After primary analysis until end of trial

IPD Sharing Access Criteria

Steering committee approval

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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