NCT04136353

Brief Summary

The purpose of this study is to determine the effectiveness of darolutamide as part of adjuvant androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) in men having radiation therapy for localised prostate cancer at very high risk of recurrence.

Trial Health

82
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,100

participants targeted

Target at P75+ for phase_3 prostate-cancer

Timeline
27mo left

Started Mar 2020

Typical duration for phase_3 prostate-cancer

Geographic Reach
6 countries

93 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress73%
Mar 2020Jul 2028

First Submitted

Initial submission to the registry

October 17, 2019

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 23, 2019

Completed
5 months until next milestone

Study Start

First participant enrolled

March 31, 2020

Completed
7.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2028

Last Updated

May 6, 2026

Status Verified

May 1, 2026

Enrollment Period

7.8 years

First QC Date

October 17, 2019

Last Update Submit

May 4, 2026

Conditions

Keywords

clinically localised prostate cancervery high riskdarolutamide

Outcome Measures

Primary Outcomes (1)

  • Metastasis-free survival

    Evidence of metastases includes findings on WBBS or CT or MRI (as reported by the site investigator) that are either characteristic of metastatic prostate cancer, and/or confirmed by other test results e.g. cytology or histopathology.

    Through study completion, an average of 5 years

Secondary Outcomes (8)

  • Overall survival

    Through study completion, an average of 5 years

  • Prostate cancer-specific survival

    Through study completion, an average of 5 years

  • PSA-progression free survival

    Through study completion, an average of 5 years

  • Time to subsequent hormonal therapy

    Through study completion, an average of 5 years

  • Time to castration-resistance

    Through study completion, an average of 5 years

  • +3 more secondary outcomes

Study Arms (2)

Darolutamide

EXPERIMENTAL

Darolutamide 600mg (2 x 300mg tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Drug: DarolutamideDrug: Luteinizing Hormone-Releasing Hormone AnalogRadiation: External Beam Radiotherapy

Placebo

PLACEBO COMPARATOR

Placebo (2 tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report. All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Drug: Placebo oral tabletDrug: Luteinizing Hormone-Releasing Hormone AnalogRadiation: External Beam Radiotherapy

Interventions

2 x 300mg oral tablets twice daily for 96 weeks

Darolutamide

2 oral tablets twice daily for 96 weeks

Placebo

All participants are to receive standard background therapy with an LHRHA, as per standard of care. The choice of LHRHA is at the discretion of the treating clinician.

DarolutamidePlacebo

All participants are to receive standard background therapy with curative-intent RT to the prostate or prostate bed as well as the pelvic lymph nodes using EBRT.

DarolutamidePlacebo

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate
  • EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following:
  • Grade Group 5, OR
  • Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA\* \> 20ng/mL, OR
  • Pelvic nodal involvement (involvement of lymph nodes (LNs) at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) OR
  • Post-radical prostatectomy ≤ 365 days prior to randomisation and planned for RT with PSA\* ≥ 0.1 ng/mL that has risen or remained stable (within ≤ 0.05 ng/mL) since a previous level at least 1 week earlier, judged to be at very high risk for recurrence based on any of the following:
  • Grade Group 5, OR
  • Grade Group 4 AND pT3a or higher, OR
  • Pelvic nodal involvement (involvement of LNs at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm) \* This PSA level must be measured within 60 days prior to randomisation. However, if a participant has already commenced endocrine therapy (ET) for prostate cancer, this PSA level must be measured within 180 days prior to commencing ET.
  • Adequate bone marrow function: Haemoglobin ≥ 100g/L, white cell count (WCC) ≥ 4.0x109/L, absolute neutrophil count (ANC) ≥ 1.5x109/L and platelets \> 100 x 109/L
  • Adequate liver function: alanine aminotransferase (ALT) \< 2 x upper limit of normal (ULN) and total bilirubin \< 1.5 x ULN, (or if total bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin)
  • Adequate renal function: calculated creatinine clearance \> 30 mL/min (Cockroft-Gault)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
  • Study treatment both planned and able to start within 7 days after randomisation
  • Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision
  • +2 more criteria

You may not qualify if:

  • Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)
  • Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation, and/or outside the pelvis (distant LNs). LN involvement is defined by histopathological confirmation, or by a short axis measurement \> 10mm on standard imaging (CT or MRI, but not PET).
  • Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of both the pelvis and the abdomen (CT or MRI), chest (CXR or CT), and a whole body radioisotope bone scan (WBBS).
  • If endocrine therapy (ET) had not started, imaging must be within 60 days prior to randomisation.
  • If ET has been started, imaging must have been performed no more than 60 days prior to starting ET and no more than 30 days after starting ET and prior to randomisation.
  • PSA \> 100 ng/mL at any time
  • Any prior use of new generation potent AR inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents).
  • Prior endocrine therapy for prostate cancer except for the following which are allowed:
  • (i) LHRHA and/or (ii) a first-generation nonsteroidal antiandrogen (NSAA) are allowed if commenced no more than 90 days before randomisation. If an NSAA has been used, it must be stopped before starting study treatment with darolutamide/placebo; and
  • Prior use of 5-alpha reductase inhibitor is allowed and if used it must be stopped before starting study treatment with darolutamide/placebo
  • Bilateral orchidectomy
  • Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT
  • History of
  • Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomisation, or
  • Significant cardiovascular disease within 6 months prior to randomisation: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade \> 2 (CTCAE v5.0), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism), coronary artery bypass graft. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (93)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute - St. Elizabeth's

Brighton, Massachusetts, 02135, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Dana Farber Cancer Institute - Milford

Milford, Massachusetts, 01757, United States

Location

XCancer Omaha/Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

New Jersey Urology Saddle Brook

Clifton, New Jersey, 07013, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

New Jersey Urology Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

New Mexico Oncology and Hematology Specialists

Albuquerque, New Mexico, 87109, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

New York University Langone Long Island

Mineola, New York, 11501, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Dayton Physicians Network

Kettering, Ohio, 45409, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

GenesisCare Newcastle

Newcastle, New South Wales, 2290, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Shoalhaven District Memorial Hospital

Nowra, New South Wales, 2541, Australia

Location

St Vincent's Public Hospital

Sydney, New South Wales, 2010, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

Location

Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

Location

Northern Cancer Institute

Sydney, New South Wales, 2065, Australia

Location

Sydney Adventist Hospital

Sydney, New South Wales, 2076, Australia

Location

Liverpool Hospital

Sydney, New South Wales, 2170, Australia

Location

St George Hospital

Sydney, New South Wales, 2217, Australia

Location

Campbelltown hospital

Sydney, New South Wales, 2560, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

ROPART

Brisbane, Queensland, 4101, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Icon Cancer Centre

Southport, Queensland, 4215, Australia

Location

Townsville Hospital

Townsville, Queensland, 4814, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Icon Cancer Centre Hobart

Hobart, Tasmania, 7000, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Peter MacCallum Cancer Centre - Bendigo Campus

Bendigo, Victoria, 3550, Australia

Location

Peter MacCallum Cancer Centre (Moorabbin Campus)

Bentleigh East, Victoria, 3165, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

GenesisCare Cabrini (Gandel Wing), Cabrini Hospital Malvern

Malvern, Victoria, 3144, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Latrobe Regional Hospital

Traralgon, Victoria, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6143, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6006, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Agency (BCCA) Fraser Valley

Surrey, British Columbia, V3V 1Z2, Canada

Location

Western Manitoba Cancer Centre - Prairie Mountain Health

Brandon, Manitoba, R7A 2B3, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Regional Health Authority B, Zone 2 Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre, St. John's

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Queen Elizabeth II Health Sciences Centre

London, Ontario, B3H 1V7, Canada

Location

Sault Area Hospital - Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Ottawa Hospital Research Institute

Toronto, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre - Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Integre de Sante et de Services Sociaux de la Monteregie Centre

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Location

Hôtel-Dieu de Québec

Québec, Quebec, G1R 2J6, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centre Hospitalier Regional de Trois-Rivieres

Québec, G8Z 3R9, Canada

Location

St. Luke's Hospital

Rathgar, Dublin 6, D06 E1C9, Ireland

Location

Cork University Hospital

Cork, T12 EC8P, Ireland

Location

Bon Secours Hospital Cork in association with UPMC Hillman Centre

Cork, T23, Ireland

Location

Mater Misericordiae University Hospital

Dublin, D07 A8NN, Ireland

Location

Mater Private Dublin

Dublin, D07 WKW8, Ireland

Location

St Luke's Radiation Oncology Network at St James's Hospital

Dublin, D08 T6T8, Ireland

Location

Beacon Private Hospital Dublin

Dublin, D18 AK68, Ireland

Location

Tallaght University Hospital

Dublin, D24 NR0A, Ireland

Location

Galway University Hospital

Galway, H91 YR71, Ireland

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Palmerston North Hospital

Palmerston North, 4442, New Zealand

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

William Harvey Hospital

Ashford, TN24 0LZ, United Kingdom

Location

Royal United Hospital Bath

Bath, BA1 3NG, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Guy's and St Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

Nottingham University Hospitals NHS Trust - Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamideGonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteins

Study Officials

  • Christopher Sweeney

    Dana-Farber Cancer Institute and Harvard Medical School

    STUDY CHAIR
  • Tamim Niazi

    Jewish General Hospital and McGill University

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 17, 2019

First Posted

October 23, 2019

Study Start

March 31, 2020

Primary Completion (Estimated)

January 31, 2028

Study Completion (Estimated)

July 31, 2028

Last Updated

May 6, 2026

Record last verified: 2026-05

Locations