A study to compare the study treatment darolutamide in combination with androgen deprivation therapy (ADT) to placebo in combination with ADT in men with elevated blood levels of a specific protein called PSA, which is a marker for high-risk of prostate cancer recurrence

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer Consumer Care AG, Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

18 Oct 2023 → ongoing

Decision date (initial)

2023-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer Consumer Care AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacokinetic, Pharmacodynamic, Safety

To determine if darolutamide plus ADT given for a pre-specified duration of 24 months improves rPFS by PSMA PET/CT compared with placebo plus ADT given for 24 months

Secondary objectives 2

1. To further evaluate efficacy and to measure the treatment impact on participant's quality of life
2. To assess the safety of darolutamide plus ADT compared with placebo plus ADT

Conditions and MedDRA coding

Biochemically recurrent prostate cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Pharmaceuticals And Medical Devices Agency, European Medicines Agency

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Capable of giving signed informed consent as described which includes compliance with the requirements, restrictions listed in the informed consent form (ICF), and in this protocol
2. Male ≥18 years of age at the time of signing the informed consent
3. Histologically or cytologically confirmed adenocarcinoma of prostate
4. Prostate cancer initially treated by: radical prostatectomy (RP) followed by adjuvant radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants who are unfit for (or refused) ART or SRT, or primary radiotherapy (RT).
5. High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen doubling time (PSADT) <12 months calculated using the formula provided by the Sponsor, and PSA ≥0.2 ng/mL after ART or SRT post RP or after RP in participants who are unfit for ART or SRT (local or central values accepted) , or PSA ≥2 ng/mL above the nadir after primary RT only (local or central values accepted).
6. Participants must undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period using either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed by BICR to identify at least one PSMA PET positive lesion of prostate cancer, and the number and the location of lesions to be used as baseline reference.
7. Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local assessment is allowed whenever central assessment cannot be done).
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received blood transfusion within 7 days prior to sample being taken); Absolute neutrophil count (ANC) ≥1.5x1^09/L (participant must not have received any growth factor within 4 weeks prior to sample being taken); Platelet count ≥100x109/L
10. Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN, (except participants with a diagnosis of Gilbert's disease); Estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 ^m2 calculated by the CKD-EPI formula
11. Sexually active male participants must agree to use contraception as detailed in the protocol during the Treatment period and for at least 1 week after the last dose of study treatment, and refrain from donating sperm during this period.

Exclusion criteria 10

1. Pathological finding consistent with small cell, ductal or ≥50 % component of neuroendocrine carcinoma of the prostate
2. History of bilateral orchiectomy
3. Metastases or recurrent /new malignant lesions in prostate gland/bed seminal vesicles, lymph nodes below the CIA bifurcation on conventional imaging (CI) as assessed by BICR during screening
4. Brain metastasis on PSMA PET /CT by BICR at screening
5. High-risk BCR after primary radiotherapy with new loco-regional lesions on screening PSMA PET/CT who are eligible for curative salvage prostatectomy
6. Prior treatment with second generation (e.g. enzalutamide, apalutamide) androgen receptor inhibitors (ARIs) and CYP 17 inhibitors (e.g., abiraterone) within 18 months prior to signing of the ICF
7. Prior treatments with PSMA-radiotherapeutics within 12 months prior to randomization
8. Prior radiotherapy (including image-guided radiotherapy) as primary, adjuvant or salvage treatment completed within 8 weeks prior to signing of the ICF
9. 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
10. History of pelvic radiotherapy for other malignancy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. rPFS by PSMA PET/CT assessed by BICR

Secondary endpoints 11

1. MFS by CI assessed by BICR
2. Time to CRPC
3. Time to initiation of first subsequent systemic antineoplastic therapy
4. Time to loco-regional progression by PSMA PET/CT
5. Time to first SSE
6. OS
7. PSA undetectable rates (<0.2 ng/mL) at 12 months
8. Time to deterioration in the FACT-P total score
9. Number of participants with TEAEs and TESAEs categorized by severity
10. Number of participants who discontinue study treatment due to a TEAE
11. Time to symptomatic progression

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer Consumer Care AG

Sponsor organisation

Bayer Consumer Care AG

Address

Peter Merian-Strasse 84

City

Basel Town

Postcode

4052

Country

Switzerland

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 2

Bayer AG

Sponsor organisation

Bayer AG

Address

-

City

Leverkusen

Postcode

51368

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Sponsor responsibilities

Article 77 compliance

Bayer Consumer Care AG

Article 77 implementation

Bayer Consumer Care AG

Locations

14 EU/EEA countries · 126 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 185 files

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

Application history

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