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 -
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Amsterdam UMC Stichting
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Number of lesions
Study Overview
Brief Summary
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.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult men (>18 years of age)
- •Any PSA, grade and stage of disease
- •Histologically proven prostate cancer
- •Patients must have a life expectancy of >12 months
- •No prior hormonal therapy (including any androgen directed treatment such as bicalutamide, apalutamide, abiraterone or enzalutamide) or taxane based chemotherapy (docetaxel or cabazitaxel)
- •Able to understand the patient information form (PIF)
- •Signed informed consent
- •Previous robot-assisted radical prostatectomy or external beam radiotherapy
- •PSMA PET/CT showing 1-5 metastases in bones and/or lymph nodes (miN1/M1ab)
Exclusion Criteria
- •A known subtype other than prostate adenocarcinoma
- •Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
- •Previous PSMA- based radioligand treatment
- •Visceral (lung, liver) or brain metastases
- •Any medical condition present that in the opinion of the investigator will affect patients’ clinical status when participating in this trial
- •Known hypersensitivity to the components of the study therapy or its analogues, specifically enzalutamide and/or darolutamide
- •Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
- •Prior hip replacement surgery potentially influencing performance of PSMA PET/CT
- •Sjogren's syndrome
- •A second active malignancy other than prostate cancer
Outcomes
Primary Outcomes
Number of lesions
Number of lesions
Size of lesions, measured in mm
Size of lesions, measured in mm
Location of lesions, distinguished in lymph node, bone, visceral, other
Location of lesions, distinguished in lymph node, bone, visceral, other
SUVmax
SUVmax
The appearance of at least 1 new PSMA-positive lesion compared to baseline PSMA PET/CT, with a SUVmax > liver (according to SPARC guidelines)
The appearance of at least 1 new PSMA-positive lesion compared to baseline PSMA PET/CT, with a SUVmax > liver (according to SPARC guidelines)
A clinical significant increase in SUVmax of existing lesions (≥20%)
A clinical significant increase in SUVmax of existing lesions (≥20%)
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)
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)
Secondary Outcomes
- Number of lesions
- Size of lesions, measured in mm
- Location of lesions, distinguished in lymph node, bone, visceral, other
- SUVmax
- Questionnaire on health-related quality of life
- Number of AE and SAE, recorded by NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Investigators
Coordinating investigator
Scientific
Amsterdam UMC Stichting