SAKK 08/23 – Addition of Darolutamide in the first-line treatment of metastatic hormone-resistant prostate cancer: a randomized phase II study
Summary description of the study
Prostate cancer is the most common type of cancer in men. Even though there have been many advances in treatment, we still need better ways to slow the progression of the disease.
When prostate cancer spreads and no longer responds to hormone treatments, it is called "metastatic hormone-resistant prostate cancer." There are several standard treatments for this condition. The main ones include:
- Chemotherapy
- Radionuclide therapy (a treatment with radioactive substances)
- Targeted oral therapy with a PARP inhibitor (a specific medication)
In this study, we look at how these standard treatments combined with an additional medication called Darolutamide affect the disease. We want to know if the combination can hold the disease longer and if it is well tolerated.
The study is randomized. This means that participants are randomly assigned to two groups. One group receives only the standard treatment, the other group receives the standard treatment plus Darolutamide.
Darolutamide is already approved in Switzerland, Europe, and the USA for the treatment of earlier stages of prostate cancer. This includes:
- Metastatic hormone-sensitive prostate cancer (cancer that has spread but still responds to hormones)
- Non-metastatic hormone-resistant prostate cancer (cancer that no longer responds to hormones but has not yet spread)
A previous study (SAKK 08/16) showed that Darolutamide is effective as maintenance therapy for advanced prostate cancer. We are now investigating whether Darolutamide can also help in an earlier stage of the disease.
(BASEC)
Intervention under investigation
In this study, participants are randomly assigned to groups. This is important to obtain reliable results from the study. This is called randomization. Each group receives a different treatment. In this study, there are 2 groups:
- Group 1 (experimental group) receives the study medication Darolutamide 2 times a day at a dosage of 2 tablets of 300 mg in addition to the standard therapy.
- Group 2 (control group) receives the standard therapy.
The study has three phases:
1) Pre-examinations: First, there are some examinations to ensure that the participants are eligible.
2) Treatment phase: This phase has two sections:
- First section: Here, participants receive either the standard therapy alone or the standard therapy together with Darolutamide (if they are in the experimental group).
- Second section: After the standard therapy, participants in the experimental group receive only Darolutamide as maintenance therapy. 3) Follow-up: After treatment, participants are further monitored to track their health.
The duration of treatment depends on how well it is tolerated and how effective it is. If the treatment is well tolerated and works, it will continue until the disease may potentially progress. While it is likely, it is not yet certain that the disease will progress.
(BASEC)
Disease under investigation
metastatic hormone-resistant prostate cancer
(BASEC)
- Diagnosis of prostate adenocarcinoma by histology or cytology
- Castration resistance: progression of the tumor after surgical removal of one or both testicles or treatment with GnRH analogs (agonist or antagonist; drugs used to artificially lower testosterone or estrogen levels in the blood)
- The patient who has not been surgically castrated consents to the continued use of GnRH analogs (agonists or antagonists) during the study.
(BASEC)
Exclusion criteria
- Presence of a small cell component
- Previous systemic therapy for metastatic castration-resistant disease
- Previous chemotherapy for metastatic hormone-sensitive prostate cancer, except for Docetaxel
(BASEC)
Trial sites
Aarau, Bellinzona, Chur, Geneva, Lausanne, Lugano, Luzern, St. Gallen, Winterthur, Zurich, Other
(BASEC)
Baden, Brugg, Davos, Ilanz, Locarno, Mendrisio, Samedan, Thusis
(BASEC)
Sponsor
Swiss Cancer Institute, Bern
(BASEC)
Contact
Contact Person Switzerland
Stefanie Röthlisberger
+41 31 389 91 91
trials@clutterswisscancerinstitute.chSwiss Cancer Institute
(BASEC)
General Information
Kantonsspital Graub?nden,Istituto Oncologico della Svizzera Italiana,
+41 31 389 91 91
trials@sakk.ch(ICTRP)
General Information
Kantonsspital GraubndenIstituto Oncologico della Svizzera Italiana
+41 31 389 91 91
trials@clutterswisscancerinstitute.ch(ICTRP)
Scientific Information
Kantonsspital Graub?nden,Istituto Oncologico della Svizzera Italiana,
+41 31 389 91 91
trials@sakk.ch(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
24.09.2024
(BASEC)
ICTRP Trial ID
NCT06401980 (ICTRP)
Official title (approved by ethics committee)
SAKK 08/23 Addition of Darolutamide to first line treatment of mCRPC: a randomized open label phase II trial (BASEC)
Academic title
Addition of Darolutamide to First Line Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): a Randomized Open Label Phase II Trial (ICTRP)
Public title
Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (ICTRP)
Disease under investigation
Metastatic Castration-resistant Prostate Cancer
(ICTRP)
Intervention under investigation
Drug: DarolutamideOther: Standard of care
(ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
(ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:<br><br> - Written informed consent according to Swiss law and ICH GCP E6(R2) regulations<br> before registration and prior to any trial specific procedures<br><br> - Histologically or cytologically confirmed diagnosis of adenocarcinoma of the<br> prostate<br><br> - Castration resistance: tumor progression after orchiectomy or during treatment with<br> GnRH analogues (agonists or antagonists).<br><br> - Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists<br> or antagonists) during the trial<br><br> - Metastatic disease, documented by imaging according to PCWG3 criteria<br><br> - Measurable disease or bone lesions that are evaluable according to PCWG3 criteria<br><br> - A minimum of 12 months on ADT+ARPI therapy (calculated from ADT initiation) within<br> mHSPC setting, showing an at least 50% PSA response or partial remission according<br> to RECIST v1.1. ARPI change within mHSPC is only allowed for intolerance.<br><br> - Progressive disease according to modified PCWG3 before registration is defined as<br> (at least 2 out of 3):<br><br> - PSA progression >= 25% above nadir (2 consecutive rises at least 3 weeks apart)<br><br> - New metastatic lesion on imaging (at least two or more new bone lesions on bone<br> scan or one new non-bone lesion or progression on PSMA-PET/CT according to<br> PROMISE V2 criteria<br><br> - Clinical progression<br><br> - Patients with a previously treated malignancy are eligible, when the risk of the<br> prior malignancy interfering with either safety or efficacy endpoints is very low<br><br> - Age >= 18 years<br><br> - WHO performance status 0-2<br><br> - Adequate bone marrow function: absolute neutrophil count >= 1.0 x 109/L, platelet<br> count >= 100 x 109/L, hemoglobin >= 90 g/L.<br><br> - Adequate hepatic function: total bilirubin <= 1.5 x ULN (except for patients with<br> Gilbert's disease <= 3.0 x ULN), ALT and AST <= 2.5 x ULN, or <= 5 x ULN under the<br> assumption that abnormal values are a result of cancer<br><br> - Adequate renal function: estimated glomerular filtration rate (eGFR) > 30<br> mL/min/1.73 m2 (according to CKD-EPI formula)<br><br> - Men agree not to donate sperm or to father a child during trial treatment and until<br> 3 months after the last dose of trial treatment<br><br> - Patients are able and willing to swallow darolutamide as whole tablet.<br><br>Exclusion Criteria:<br><br> - Presence of a small cell component<br><br> - Prior systemic therapy for metastatic castration-resistant disease<br><br> - Prior chemotherapy for mHSPC, except docetaxel<br><br> - Prior LuPSMA or radium 223 for prostate cancer<br><br> - Concomitant or recent (within 28 days of registration) treatment with any other<br> experimental drug<br><br> - Concomitant use of other anti-cancer drugs or radiotherapy except for local pain<br> control and GnRH analogues<br><br> - Severe or uncontrolled cardiovascular disease<br><br> - Acute exacerbations of chronic illnesses, serious infections, or major surgery<br> within 28 days before expected start of treatment<br><br> - Clinical or radiological evidence of current spinal cord compression<br><br> - Any concomitant drugs contraindicated for use with darolutamide according to the<br> approved product information<br><br> - Known hypersensitivity to darolutamide<br><br> - Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI<br> absorption or tolerance of darolutamide<br><br> - Any other serious underlying medical, psychiatric, psychological, familial or<br> geographical condition, which in the judgment of the investigator may interfere with<br> the planned staging, treatment and follow-up, affect patient compliance or place the<br> patient at high risk from treatment-related complications.
(ICTRP)
not available
Primary and secondary end points
Radiographic progression-free survival (rPFS)
(ICTRP)
Overall survival (OS);Time to symptomatic/clinical progression;Time to PSA progression;Event-free survival (EFS);Objective response rate according to RECIST;PSA response (30%, 50%, 90% and best);Duration of PSA response (50%)
(ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Richard Cathomas, Prof;Ursula Vogl, MD;Simone Rahel Wyss-Neyer, trials@sakk.ch, +41 31 389 91 91, Kantonsspital Graub?nden,Istituto Oncologico della Svizzera Italiana, (ICTRP)
Secondary trial IDs
SAKK 08/23 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT06401980 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available