Clinical Application of the Androgen Receptor Inhibitor Darolutamide to Upregulate the Prostate-Specific Membrane Antigen (PSMA) Protein Expression in Patients with Hormone Sensitive Prostate Cancer. - The DARO-flare Trial -

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Diseases [C] - Male Urogenital Diseases [C12]

Decision date (initial)

2025-12-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer B.V.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To prospectively investigate whether the ‘darolutamide FLARE phenomenon’, observed after the administration of the second line ARTA darolutamide in patients with prostate cancer, results in 1) a higher number of PSMA expressing prostate cancer deposits (either defined as local residual disease or metastatic disease) or 2) in a higher expression of PSMA in individual lesions (determined by SUVmax) on PSMA PET/CT.

Secondary objectives 2

1. To assess the absolute number and the relative number of patients in whom a treatment change is observed by renewed imaging by PSMA PET/CT after a short (7 or 14 days) course of administration with darolutamide (‘darolutamide FLARE’)
2. To assess the patient-reported toxicity and side-effects of a short course of administration with the study medication, the second line ARTA darolutamide.

Conditions and MedDRA coding

Prostate cancer

Regulatory references

Plan to share IPD

No

IPD plan description

Not applicable.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adult men (>18 years of age)
2. Any PSA, grade and stage of disease
3. Histologically proven prostate cancer
4. ECOG 0-1
5. Patients must have a life expectancy of >12 months
6. No prior hormonal therapy (including any androgen directed treatment such as bicalutamide, apalutamide, abiraterone or enzalutamide) or taxane based chemotherapy (docetaxel or cabazitaxel)
7. Able to understand the patient information form (PIF)
8. Signed informed consent
9. Cohort 1 - Previous robot-assisted radical prostatectomy or external beam radiotherapy
10. Cohort 1 - PSMA PET/CT showing 1-5 metastases in bones and/or lymph nodes (miN1/M1ab)
11. Cohort 2 - Patients with biochemical recurrent disease PSA 0.5-1.0 ng/mL (2 times) after RARP
12. Cohort 2 - miN0M0 on re-staging PSMA PET/CT

Exclusion criteria 10

1. A known subtype other than prostate adenocarcinoma
2. Previous PSMA- based radioligand treatment
3. Visceral (lung, liver) or brain metastases
4. Any medical condition present that in the opinion of the investigator will affect patients’ clinical status when participating in this trial
5. Known hypersensitivity to the components of the study therapy or its analogues, specifically enzalutamide and/or darolutamide
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
7. Prior hip replacement surgery potentially influencing performance of PSMA PET/CT
8. Sjogren's syndrome
9. A second active malignancy other than prostate cancer
10. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. Number of lesions
2. Size of lesions, measured in mm
3. Location of lesions, distinguished in lymph node, bone, visceral, other
4. SUVmax
5. Cohort 1 - The appearance of at least 1 new PSMA-positive lesion compared to baseline PSMA PET/CT, with a SUVmax > liver (according to SPARC guidelines)
6. Cohort 1 - A clinical significant increase in SUVmax of existing lesions (≥20%)
7. Cohort 1 - An increase in the total number of metastatic lesions above 5 compared to baseline PSMA PET/CT (shifting from an oligo-metastatic to poly-metastatic disease stage)
8. Cohort 2 - The appearance of at least 1 metastatic lesion (lymph node or bone) suspicious for prostate cancer with a SUVmax > liver (according to SPARC guidelines)
9. Cohort 2 - The detection of local recurrence of disease in the absence of metastatic disease with a SUVmax > liver (according to SPARC guidelines)
10. Cohort 2 - The detection of local recurrence of disease with local or a metastatic lesion suspicious for prostate cancer with either of the two having a SUVmax > liver (according to SPARC guidelines)

Secondary endpoints 6

1. Number of lesions
2. Size of lesions, measured in mm
3. Location of lesions, distinguished in lymph node, bone, visceral, other
4. SUVmax
5. Questionnaire on health-related quality of life
6. Number of AE and SAE, recorded by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Coordinating investigator

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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