Study Completed

Prostatic Neoplasms

Bayer Identifier:

21140

ClinicalTrials.gov Identifier:

NCT04736199

EudraCT Number:

2020-003093-48

EU CT Number:

2022-502244-12-00

Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer

Trial purpose

The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.

Key Participants Requirements

Sex

Male

Age

18 - N/A (No Limit)

Inclusion Criteria

- Histologically or cytologically confirmed adenocarcinoma of prostate
- Metastatic disease
- Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti–androgen, but not earlier than 12 weeks before randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
- Adequate bone marrow, liver and renal function

Exclusion Criteria

- Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second–generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancer treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization; Radiopharmaceuticals; Any other anti-cancer treatment for prostate cancer, excluding local therapies and
ADT.
- Treatment with radiotherapy within 2 weeks before randomization
- Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s)
- Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
- Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
- A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
- Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization
- Inability to swallow oral medications

Trial summary

Enrollment Goal

666

Trial Dates

February 2021 - January 2026

Phase

Phase III

Could I Receive a placebo

Yes

Products

Darolutamide, BAY 1841788

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Hospital San Pedro De Alcantara \| Oncologia	Cáceres, 10003, Spain
Completed	Parc Tauli Hospital Universitari \| Oncologia	Barcelona, 08208, Spain
Completed	Fundacio Puigvert \| Urologia	Barcelona, 08025, Spain
Completed	Hospital Universitario Virgen De La Victoria \| Urologia	Málaga, 20910, Spain
Completed	Hospital Universitario Fundacion Alcorcon \| Urologia	Alcorcón, 28922, Spain
Completed	Hospital Universitario Virgen Del Rocio S.L. \| Urologia	Sevilla, 41013, Spain
Completed	G. Kenneth Jansz Medicine Professional Corporation	Burlington, L7N 3V2, Canada
Completed	Centre Hospitalier de l'Universite de Montreal (CHUM) \| Centre de Recherche	Montreal, H2X 0A9, Canada
Completed	Cape Town Oncology Trials	Cape Town, 7570, South Africa
Completed	Cancercare Langenhoven	Port Elizabeth, 6045, South Africa
Completed	University of Pretoria, Clinical Research Unit	Pretoria, 2, South Africa
Completed	East Rand Medical Research Unit	Pretoria, 1475, South Africa
Completed	Peninsula Oncology Centre	Frankston, 3199, Australia
Completed	Nepean Hospital	Kingswood, 2747, Australia
Completed	Austin Health	Heidelberg, 3084, Australia
Completed	Macquarie University Hospital - Oncology Department	Sydney, 2109, Australia
Completed	Northern Cancer Institute	St Leonards, 2065, Australia
Completed	Cancer Research South Australia	Adelaide, 5000, Australia
Completed	Hospital Clínico de la Pontificia Univ. Católica de Chile	Santiago, 8320165, Chile
Completed	Centro de Investigación Clínica del Sur	Temuco, 4781156, Chile
Completed	UROMED	Santiago, 7500787, Chile
Completed	Fundación Arturo López Perez	Santiago, 7500921, Chile
Completed	OncoCentro	Viña del Mar, 2520598, Chile
Completed	Centro de Estudios Clínicos SAGA SpA	Providencia, 7520349, Chile
Completed	Oncovida	Santiago, 7510032, Chile
Completed	Hospital Mae de Deus	Porto Alegre, 90850-170, Brazil
Completed	IBCC - Instituto Brasileiro de Controle do Cancer	Jaú, 03102-002, Brazil
Completed	Hosp. Araujo Jorge da Associação de Combate ao Câncer	Goiânia, 74605-070, Brazil
Completed	Santa Casa de Porto Alegre \| Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia	Jaú, 90020-090, Brazil
Completed	Liga Norte Riograndense Contra o Cancer \| Centro de Pesquisa Clínica	Natal, 59040-000, Brazil
Completed	Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner	Curitiba, 81520-060, Brazil
Completed	Inst. de Assistência Médica ao Sérvidor Público Estadual	São Paulo, 04039-004, Brazil
Completed	Hospital de Base \| Funfarme - Centro Integrado de Pesquisa - Cardiologia	São José do Rio Preto, 15090-000, Brazil
Completed	Instituto COI de Educação e Pesquisa	Rio de Janeiro, 22793-080, Brazil
Completed	FZ Pesquisa e Servicos em Cardiologia \| Porto Alegre, Brazil	Porto Alegre, 91350-280, Brazil
Completed	Hospital da Universidade Federal de Minas Gerais	Belo Horizonte, 30130-100, Brazil
Completed	Urobrasil	São Paulo, 01243-020, Brazil
Completed	Cetus Oncologia Hospital Dia	São Paulo, 30150-270, Brazil
Completed	Fundacao Pio XII – Hospital de Cancer de Barretos	Barretos, 14784-400, Brazil
Completed	Unidade de Pesquisas Clinicas em Oncologia	Pelotas, 96020-080, Brazil
Completed	Assistência Multidisciplinar em Oncologia (AMO)	Salvador, 41950-640, Brazil
Completed	Chelyabinsk Regional Oncology Dispensary	Chelyabinsk, 454087, Russia
Completed	Sverdlovsk Regional Clinical Hospital #1	Yekaterinburg, 620102, Russia
Completed	Clinical Oncological Dispensary of Omsk Region	Omsk, 644013, Russia
Completed	Republican Clinical Oncology Dispensary	Ufa, 450054, Russia
Completed	AV Medical Group	Saint Petersburg, 196006, Russia
Completed	Russian Scientific Radiology and Surgery Technologies Center	Saint Petersburg, 197758, Russia
Completed	Volga District Med Center FMBA	Nizhny Novgorod, 603109, Russia
Completed	Republican Clinical Oncology Dispensary	Ufa, 450054, Russia
Completed	Arkhangelsk Clinical Oncology Dispensary	Arkhangelsk, 163045, Russia
Completed	LLC Reafan	Novosibirsk, 630099, Russia
Completed	Multi-Field Clinical Medical Center "Medical City"	Tyumen, 625041, Russia
Completed	Vologda Regional Hospital	Vologda, 160022, Russia
Completed	Ivanovo Regional Oncology Dispensary	Ivanovo, 153040, Russia
Completed	Republican Clinical Oncology Dispensary Kazan	Kazan, 420029, Russia
Completed	Ltd "EVIMED"	Chelyabinsk, 454048, Russia
Completed	Medical Center "Avicenna"	Novosibirsk, 630099, Russia
Completed	Research Centre of X-ray and Radiology	Moscow, 117997, Russia
Completed	Scientific Research Instutute of Oncology n.a. N.N. Petrov	Saint Petersburg, 197758, Russia
Completed	City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA	Dnipro, 49102, Ukraine
Completed	Kyiv City Hospital #3 - Department of Urology	Kyiv, 02660, Ukraine
Completed	Kyiv Regional Oncological Dispensary	Kyiv, 4107, Ukraine
Completed	CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"	Cherkasy, 18009, Ukraine
Completed	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing, 100000, China
Completed	Anhui Provincial Hospital	Hefei, 230031, China
Completed	Beijing Hospital	Beijing, 100730, China
Completed	Beijing Cancer Hospital - Oncology Department	Beijing, 100142, China
Completed	Guangzhou First People Hospital	Guangzhou, 510180, China
Completed	The 1st Affiliated Hospital of Zhejiang University	Hangzhou, 310000, China
Completed	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing, 210008, China
Completed	The 2nd Affiliated Hospital of Soochow University	Suzhou, 215004, China
Completed	SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos	Chengdu, 610072, China
Completed	Yantai Yuhuangding Hospital	Yantai, 264000, China
Completed	Peking University Third Hospital	Beijing, 100083, China
Completed	Liaoning Cancer Hospital and Institute	Shenyang, 110042, China
Completed	Sun Yat-sen University Cancer Center	Guangzhou, 510000, China
Completed	Hunan Cancer Hospital - Oncology Department	Changsha, 410013, China
Completed	Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.	Wuhan, 430030, China
Completed	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou, 325000, China
Completed	Zhongnan hospital ,Wuhan University	Wuhan, 430071, China
Completed	ZheJiang Provincial People's Hospital	Hangzhou, 310014, China
Completed	1st Hospital of Jilin University	Changchun, 130021, China
Completed	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an, 710061, China
Completed	Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center	Shenzhen, 518172, China
Completed	Hubei Cancer Hospital	Wuhan, 430079, China
Completed	Sichuan University West China Hospital	Chengdu, 610041, China
Completed	Ningbo First Hospital	Ningbo, 315010, China
Completed	Nantong tumor hospital	Nantong, 226361, China
Completed	The Hospital of Lithuanian University of Health SciencesLUHS	Kaunas, LT-50009, Lithuania
Completed	Vilnius University Hospital Santaros Klinikos	Vilnius, LT-08661, Lithuania
Completed	National Cancer Institute	Vilnius, LT-08660, Lithuania
Completed	PI Klaipedos University Hospital	Klaipeda, LT-92288, Lithuania
Completed	Sawami Man Singh (SMS) Medical College & Attached Hospitals	Jaipur, 302017, India
Completed	Sparsh Hospital & Critical Care	Bhubaneswar, 751007, India
Completed	Tata Medical Center	Kolkata, 700156, India
Completed	Regional Cancer Centre - Thiruvananthapuram	Thiruvananthapuram, 695011, India
Completed	HCG Cancer Centre - Ahmedabad	N/A, 380060, India
Completed	Healthcare Global Enterprises Ltd	Bengaluru, 560027, India
Completed	Curie Manavata Cancer Centre	Nashik, 422004, India
Completed	Christian Medical Center & Hospital	N/A, 141008, India
Completed	Rajiv Gandhi Cancer Institute & Research Centre	New Delhi, 110085, India
Completed	Cancer Care Clinic - Vadodara	N/A, 390007, India
Completed	All India Institute of Medical Sciences	Bhubaneswar, 751019, India
Completed	Jehangir Hospital	Pune, 411001, India
Completed	Post Graduate Institute of Medical Education and Research	Chandigarh, 160012, India
Completed	Jaslok Hospital and Research Centre	Mumbai, 400026, India
Completed	Meenakshi Mission Hospital & Research Centre	Madurai, 625107, India
Completed	Amrita Institute of Medical Sciences	Kochi, 682041, India
Completed	Mahatma Gandhi Cancer Hospital & Research Institute	Visakhapatnam, 530017, India
Completed	Jawaharlal Institute Of Postgraduate Medical Education and R	Gorimedu, 605006, India
Completed	Marathwada Regional Cancer Centre and Research Institute	Aurangabad, 431001, India
Completed	K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre	Belgaum, 590010, India
Completed	Apollo Speciality Hospitals	Madurai, 625020, India
Completed	The Gujarat Cancer & Research Institute	Ahmedabad, 380016, India
Completed	Apex Wellness Hospital	Nashik, 422009, India
Completed	Taipei Veterans General Hospital	Taipei, 11217, Taiwan
Completed	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung, 807377, Taiwan
Completed	Taichung Veterans General Hospital	Taichung, 40705, Taiwan
Completed	Changhua Christian Hospital	Changhua City, 50006, Taiwan
Completed	National Cheng Kung University Hospital	Tainan, 704, Taiwan
Completed	Aliada	San Isidro, 15036, Peru
Completed	Hospital Guillermo Almenara Irigoyen	Santiago de Surco, 15033, Peru
Completed	Hospital Militar Luis Arias Schreiber	Lima, 15076, Peru
Completed	Clínica El Golf	Lima, 15073, Peru
Completed	Canterbury Urology Research Trust	Christchurch, 8013, New Zealand
Completed	Tauranga Urology Research Limited	Tauranga, 3112, New Zealand
Completed	Waikato Hospital	Hamilton, 3240, New Zealand
Completed	Waikato Hospital	Hamilton, 3240, New Zealand
Completed	Daugavpils Regional Hospital	Daugavpils, LV-5417, Latvia
Completed	URO Ltd.	Riga, LV-1006, Latvia
Completed	Vidzemes Hospital	Valmiera, LV-4201, Latvia
Completed	P. Stradins Clinical University Hospital	Riga, LV-1002, Latvia
Completed	RAKUS Hospital Gailezers	Riga, 1038, Latvia

Primary Outcome

Radiological Progression-free Survival (rPFS) Assessed by Central Review
rPFS used conventional imaging method (99mTc-phosphonate bone scan, CT/MRI scan). rPFS was defined as the time from the date of randomization to the date of progressive disease in malignant soft tissue lesions, progressive disease in malignant bone lesions, or death due to any cause, whichever occurs first. Malignant soft tissue lesions were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and malignant bone lesions were assessed by Prostate Cancer Clinical Trials Working Group (PCWG3) criteria.
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months

Secondary Outcome

Overall Survival (OS)
Time from the date of randomization to the date of death from any cause.
Time Frame:
From randomization to the final analysis date, approximately 47 months
Time to Castration-Resistant Prostate Cancer (CRPC)
Time from the date of randomization to the date of first castration resistant event (radiological progression, Prostate-specific antigen (PSA) progression or symptomatic skeletal events, whichever occurs first).
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Initiation of Subsequent Anti-cancer Therapy
Time from the date of randomization to initiation of first subsequent anti-cancer therapy for prostate cancer.
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to PSA Progression
Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression with serum testosterone being at castrate level <0.50 ng/mL, is defined as a ≥25% increase above the nadir (lowest at or after baseline) value and an increase in absolute value of ≥2 ng/mL above nadir, and is at least 12 weeks from randomization date, which is confirmed by a second value 3 or more weeks later. All PSA values between the initial assessment meeting the PSA progression criteria and confirmation assessment must be ≥2 ng/mL and ≥25% increase above nadir, serum testosterone at castrate levels <0.50 ng/mL is requested at initial assessment.
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months
PSA Undetectable Rates (<0.2 ng/mL)
Percentage of subjects with detectable PSA values of ≥0.2 ng/mL at baseline which became undetectable with any PSA values <0.2 ng/mL during the period between randomization and 30 days after last dose of study drug or start of new anti-cancer therapy whichever occurred earliest, based on the subjects had detectable PSA value at baseline.
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Pain Progression
Pain progression was assessed by Question 3 (Q3) of the BPI–SF questionnaire related to the worst pain in the last 24 hours (worst pain subscale [WPS]) taken as an average for post baseline score, or initiation of short or long-acting opioids for malignant disease for ≥7 consecutive days after randomization. Pain progression was defined as: (1) for asymptomatic subjects with WPS=0 at baseline, an increase of 2 or more points in the WPS score from nadir observed at 2 consecutive evaluations ≥4 weeks apart, or initiation of short- or long-acting opioid use for malignant disease for ≥7 consecutive days after randomization; (2) for symptomatic subjects with WPS >0 at baseline, an increase of 2 or more points in the WPS score from nadir observed at 2 consecutive evaluations ≥4 weeks apart and a WPS ≥5, or initiation of short- or long-acting opioid use for malignant disease for ≥7 consecutive days after randomization.
Time Frame:
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Number of Participants With Adverse Events as a Measure of Safety
An AE is any untoward medical occurrence in a patient or clinical study participant, after providing written IC for participation in the study, may or may not be temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AE (TEAE) is defined as any event arising or worsening after the first dose of study drug until 30 days after the last dose of study drug.
Time Frame:
From start of study drug administration until 30 days after the last administration

Trial design

A randomized, double-blind, placebo-controlled Phase 3 study of darolutamide in addition to androgen deprivation therapy (ADT) versus placebo plus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC).

Trial Type

Interventional

Intervention Type

Other

Trial Purpose

Treatment

Allocation

Randomized

Blinding

Double-blind

Assignment

Parallel

Trial Arms

Additional Information

Click here to find further information and, after study completion, the study results according to Bayer's transparency standards