Darolutamide vs ADT in hormone naïve Pca

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2017 → ongoing

Decision date (initial)

2024-05-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Organisation for Research and Treatment of Cancer (EORTC) · Bayer HealthCare Pharmaceuticals Inc.

External identifiers

EU CT number

2024-510840-30-00

EudraCT number

2016-004334-17

ClinicalTrials.gov

NCT02972060

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary trial objective is to demonstrate that darolutamide produces prostate-specific antigen (PSA) response rates at 24 weeks (defined as ≥ 80% reduction compared to baseline) that are in the range of those achieved with 24 weeks of ADT.

Secondary objectives 8

1. To document the effects of darolutamide compared to ADT in terms of patient-reported side effects of hormonal therapy, based on the HTR symptom scale of EORTC QLQ PR25 at 24 weeks
2. To document the effects of darolutamide compared to ADT in terms of patient-reported side effects of hormonal therapy, based on EORTC QLQ C30 and PR25 at 24 weeks
3. To document the effect of darolutamide on PSA complete response rate at 24 weeks (defined as ≥ 90% reduction compared to baseline)
4. To document the effect of darolutamide on objective response rate at 24 weeks in patients with RECIST 1.1 measurable disease at baseline
5. To document the safety and tolerability of darolutamide vs. ADT in subjects who have not previously received hormone treatment for prostate cancer
6. To document the effects of darolutamide on androgen deprivations symptoms using the AMS questionnaires
7. To document the proportion of patients who opted to continue treatment with darolutamide beyond the 24 weeks evaluation time point
8. To document the safety of darolutamide in subjects benefiting from treatment beyond the 96 weeks evaluation time point.

Conditions and MedDRA coding

Hormone Naive Prostate Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Aged 18 years or older
2. Histologically confirmed prostate cancer (all stages) for whom continuous ADT is indicated for a minimum period of 24 weeks
3. M0 patients or those presenting with a maximum of 4 confirmed metastatic lesions, including bone, extra-pelvic lymph nodes, and > 2 cm pelvic lymph nodes by imaging (contrast enhanced CT scans or MRI, Tc-99m BS according to local practice, see section 6.1.1). Visceral metastases are excluded
4. Asymptomatic for metastatic prostate cancer; urinary symptoms are allowed
5. Baseline total testosterone ≥ 8 nmol/L or 230 ng/dL
6. Two subsequent PSA values ≥ 2 ng/ml, done in the past 3 months (prior to enrollment) with a minimum of 2 weeks between the two, with the second being equal to or higher than the first
7. WHO performance status (PS) of 0-1
8. G8 score ≥ 14 for patients aged ≥ 70 years old
9. A life expectancy of at least 12 months
10. Able to swallow the study drug whole as a tablet
11. Adequate bone marrow function • absolute neutrophil count (ANC) ≥ 1.5 109/L. • hemoglobin ≥ 10.0 g/dl. • platelets ≥ 100 109/L.
12. Adequate renal function: creatinine ≤ 1.5 x ULN
13. Albumin > 25 g/L
14. Adequate hepatic function: • Bilirubin: total bilirubin ≤ 1.5 × upper limit of normal (ULN). • AST and/or ALT ≤ 2.5 × ULN.
15. Normal 12-lead ECG as per local standard
16. Patients of reproductive potential should use adequate birth control measures, during the study treatment period and for at least 3 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
17. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
18. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria 12

1. Previously or currently receiving hormonal therapy with intent to treat prostate cancer disease (surgical castration or other hormonal manipulation, e.g. LHRH agonists, LHRH antagonists, anti-androgens, oestrogens, 5α-reductase inhibitor). For patients that have received (neo)adjuvant ADT before radiotherapy, it should have been stopped for more than 1 year
2. Prior use of investigational agents that block androgen synthesis or block androgen receptor
3. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto)
4. Has received systemic glucocorticoids within 24 weeks prior to enrollment or is expected to require systemic glucocorticoids during the study period, unless determined to be medically necessary by the investigator for other indications than prostate cancer
5. Radiation therapy for treatment of the primary tumor within 3 months prior to enrollment
6. Use of an investigational agent within 4 weeks prior to enrollment is not allowed
7. Gastrointestinal disorder affecting absorption (e.g. gastrectomy, active peptic ulcer disease) within 3 months prior to enrollment
8. Known hypersensitivity to the study treatment or any of its ingredients (refer to Investigator's brochure).
9. Severe or uncontrolled concurrent disease, infection or co-morbidity including active viral hepatitis, known human immunodeficiency virus infection with detectable viral load (HIV) or chronic liver disease (Child Pugh C)
10. History of prior malignancy. 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 other cancer from which the patient has been disease-free for a period of at least 5 years.
11. Clinically significant cardiovascular disease including: • Myocardial infarction within 6 months prior to randomization • Uncontrolled angina within 3 months prior to randomization • Coronary/peripheral artery bypass within 6 months prior to randomization • Stroke within 6 months prior to randomization • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45% • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
12. Uncontrolled hypertension as indicated by a resting systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg at the screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the PSA response assessed at 24 weeks. PSA response is defined as a ≥ 80% decline in PSA measurement taken at week 24 relative to the measurement taken at baseline, in the darolutamide study arm. The ADT arm is used as an internal control.

Secondary endpoints 4

1. The main key secondary endpoint in this study is the change in hormone-treatment related symptoms scale of the EORTC QLQ-PR25 at 24 weeks compared to baseline in the darolutamide study arm. A 10-point difference is regarded as a clinically meaningful benefit.
2. Safety according to NCI-CTC version 4.0
3. Objective response rate at 24 weeks in patients with RECIST 1.1 measurable disease at baseline
4. PSA complete response rate at 24 weeks defined as a ≥ 90% decline in PSA measurement at week 24 relative to the measurement taken at baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 2

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications