Trial Title:
Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
NCT ID:
NCT06401980
Condition:
Metastatic Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
Metastatic Castration-Resistant Prostate Cancer
mCRPC
Darolutamide
phase II trial
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
International, randomized, open label, phase II study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Darolutamide
Description:
Darolutamide will be supplied in bottles as 300 mg film-coated tablets for oral intake
Arm group label:
Arm A: Experimental
Other name:
Nubeqa®
Intervention type:
Other
Intervention name:
Standard of care
Description:
- Docetaxel
- Cabazitaxel
- LuPSMA
- Radium 223
- Olaparib, in case of BRCA1 or 2 mutated or HRR deficient tumors
The standard of care is chosen by the local investigator and respecting the country
specific approvals.
Arm group label:
Arm B: Control
Summary:
Despite improvements in treatment, metastatic prostate cancer remains incurable,
especially in the case of pretreated metastatic castration-resistant disease (mCRPC),
where treatment options are limited, leading to an unmet need. The paradigm shift in the
treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has affected the
treatment landscape for mCRPC patients. Many have already received androgen deprivation
therapy (ADT) and androgen receptor pathway inhibitors (ARPI), making first-line mCRPC
treatment challenging.
The Swiss Group for Clinical Cancer Research (SAKK) has shown in previous studies that
maintenance treatment with an ARPI, such as darolutamide, can improve radiographic
progression-free survival (rPFS) in pretreated mCRPC patients. In the SAKK 08/16 trial,
darolutamide maintenance was found to prolong PFS compared to placebo, especially in
patients who responded well to prior ARPI treatment.
Based on these findings, the hypothesis is that continued AR-pathway blockade with
darolutamide, initiated in patients progressing from mHSPC to mCRPC on ARPI treatment,
can improve outcomes when added to standard first-line mCRPC therapy and continued as
maintenance. The proposed study aims to evaluate the efficacy of darolutamide, combined
with physician-choice standard of care (including taxane chemotherapy, olaparib, radium
223, or LuPSMA), followed by maintenance therapy, on rPFS for patients in the first-line
setting of mCRPC.
Detailed description:
Metastatic prostate cancer remains incurable despite several major improvements in the
treatment. In the case of pretreated metastatic castration-resistant disease (mCRPC) the
options remain scarce and there is still an unmet need in this patient population.
For the majority of patients with metastatic hormone-sensitive prostate cancer (mHSPC)
the combination of androgen deprivation (ADT) and ARPI (or even a triplet treatment with
ADT, docetaxel and darolutamide or abiraterone) has become standard of care. However,
when patients become metastatic castration resistant (mCRPC) over time a change of
systemic treatment is necessary and thus this paradigm switch in treatment of mHSPC has
had a major impact on treatment of mCRPC patients. Many patients developing metastatic
castration-resistant disease these days have not only received ADT but also an ARPI and,
in some cases, also docetaxel. Therefore, the treatment options in the first line setting
of mCRPC are restricted and the outcome is poorer compared to the past. Improvement of
first line mCRPC is an important unmet clinical need.
The SAKK has demonstrated in two earlier studies that maintenance treatment with an ARPI
(orteronel in SAKK 08/11 or darolutamide in SAKK 08/16) can improve radiographic
progression-free survival in pretreated mCRPC patients after ARPI and/or taxane based.
This maintenance concept could be introduced more generally in the first line setting of
mCRPC.
In the SAKK 08/16 trial, darolutamide maintenance was shown to prolong progression-free
survival (PFS) compared to placebo, in patients with mCRPC who had received prior ARPI,
and whose disease did not progress during taxane therapy. This benefit was more
pronounced in patients with prior response to ARPI.
Taken together it is hypothesized that the continued AR-pathway blockade with
darolutamide in patients progressing from mHSPC to mCRPC on ARPI treatment can improve
outcome when it is added to a standard first line mCRPC therapy and then continued as
maintenance. SAKK proposes to add the ARPI darolutamide to standard first line mCRPC
treatment consisting of either taxane chemotherapy (docetaxel or cabazitaxel), olaparib,
radium 223 or LuPSMA. The choice of standard of care treatment is up to the investigator,
respecting the country specific approvals. Darolutamide will be given concomitantly with
the chosen first line treatment and will be continued as maintenance afterwards until
radiographic progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent according to Swiss law and ICH GCP E6(R2) regulations
before registration and prior to any trial specific procedures
- Histologically or cytologically confirmed diagnosis of adenocarcinoma of the
prostate
- Castration resistance: tumor progression after orchiectomy or during treatment with
GnRH analogues (agonists or antagonists).
- Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists
or antagonists) during the trial
- Metastatic disease, documented by imaging according to PCWG3 criteria
- Measurable disease or bone lesions that are evaluable according to PCWG3 criteria
- One line of previous ARPI therapy (abiraterone, enzalutamide, darolutamide,
apalutamide) for at least 18 months within mHSPC setting, showing an at least 50%
PSA response or partial remission according to RECIST v1.1
- Progressive disease according to PCWG3 before registration is defined as (at least 2
out of 3):
- PSA progression≥ 25% and ≥ 2 ng/mL above nadir (2 consecutive rises at least 3
weeks apart)
- New metastatic lesion on imaging (at least two or more new bone lesions on bone
scan or one new non-bone lesion)
- Clinical progression
- Patients with a previously treated malignancy are eligible, when the risk of the
prior malignancy interfering with either safety or efficacy endpoints is very low
- Age ≥ 18 years
- WHO performance status 0-2
- Adequate bone marrow function: absolute neutrophil count ≥ 1.0 x 109/L, platelet
count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L.
- Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with
Gilbert's disease ≤ 3.0 x ULN), ALT and AST ≤ 2.5 x ULN, or ≤ 5 x ULN under the
assumption that abnormal values are a result of cancer
- Adequate renal function: estimated glomerular filtration rate (eGFR) > 30
mL/min/1.73 m2 (according to CKD-EPI formula)
- Men agree not to donate sperm or to father a child during trial treatment and until
3 months after the last dose of trial treatment
- Patients are able and willing to swallow darolutamide as whole tablet.
Exclusion Criteria:
- Presence of a small cell component
- Prior systemic therapy for metastatic castration-resistant disease
- Prior chemotherapy for mHSPC, except docetaxel
- Prior LuPSMA or radium 223 for prostate cancer
- Concomitant or recent (within 28 days of registration) treatment with any other
experimental drug
- Concomitant use of other anti-cancer drugs or radiotherapy except for local pain
control and GnRH analogues
- Severe or uncontrolled cardiovascular disease
- Acute exacerbations of chronic illnesses, serious infections, or major surgery
within 28 days before expected start of treatment
- Clinical or radiological evidence of current spinal cord compression
- Any concomitant drugs contraindicated for use with darolutamide according to the
approved product information
- Known hypersensitivity to darolutamide
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI
absorption or tolerance of darolutamide
- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Kantonsspital Baden
Address:
City:
Baden
Zip:
5404
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Andreas Erdmann, MD
Phone:
+41 56 486 27 62
Email:
andreas.erdmann@ksb.ch
Investigator:
Last name:
Andreas Erdmann, MD
Email:
Principal Investigator
Facility:
Name:
Istituto Oncologico della Svizzera Italiana (IOSI)
Address:
City:
Bellinzona
Zip:
6500
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Ursula Vogl, MD
Phone:
+41 91 811 84 63
Email:
ursula.vogl@eoc.ch
Investigator:
Last name:
Ursula Vogl, MD
Email:
Principal Investigator
Facility:
Name:
Inselspital
Address:
City:
Bern
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Dilara Akhoundova, MD
Phone:
+41 31 63 2 03 91
Email:
dilara.akhoundovasanoyan@insel.ch
Investigator:
Last name:
Dilara Akhoundova Dilara Akhoundova, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Graubuenden
Address:
City:
Chur
Zip:
7000
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Richard Cathomas, MD
Phone:
41-81-256-6695
Email:
richard.cathomas@ksgr.ch
Investigator:
Last name:
Richard Cathomas, MD
Email:
Principal Investigator
Facility:
Name:
Hôpitaux Universitaires Genève HUG
Address:
City:
Genève
Zip:
1211
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Petros Tsantoulis, MD
Phone:
+41 79 553 23 53
Email:
petros.tsantoulis@hcuge.ch
Investigator:
Last name:
Petros Tsantoulis, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Universitaire Vaudois CHUV
Address:
City:
Lausanne
Zip:
CH-1011
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Dominik Berthold, MD
Phone:
+41 21 314 80 83
Email:
dominik.berthold@chuv.ch
Investigator:
Last name:
Dominik Berthold, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital St. Gallen
Address:
City:
St. Gallen
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Stefanie Fischer, MD
Phone:
+41 71 494 11 11
Email:
stefanie.fischer@kssg.ch
Investigator:
Last name:
Stefanie Fischer, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Winterthur
Address:
City:
Winterthur
Zip:
CH-8400
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Miklos Pless, Prof.
Phone:
41-52-266-2552
Email:
miklos.pless@ksw.ch
Investigator:
Last name:
Miklos Pless, Prof.
Email:
Principal Investigator
Facility:
Name:
UniversitaetsSpital Zuerich
Address:
City:
Zurich
Zip:
8091
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Anja Lorch, Prof
Phone:
+41 44 255 22 14
Email:
anja.lorch@usz.ch
Investigator:
Last name:
Anja Lorch, Prof
Email:
Principal Investigator
Facility:
Name:
OnkoZentrum Zürich - Standort Seefeld
Address:
City:
Zürich
Zip:
8038
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Aurelius Omlin, MD
Phone:
+41 43 344 33 33
Email:
aurelius.omlin@ozh.ch
Investigator:
Last name:
Aurelius Omlin, MD
Email:
Principal Investigator
Facility:
Name:
Stadtspital Triemli Zürich
Address:
City:
Zürich
Zip:
8063
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Katharina Hoppe, MD
Phone:
+41 44 416 34 91
Email:
katharina.hoppe@stadtspital.ch
Investigator:
Last name:
Katharina Hoppe, MD
Email:
Principal Investigator
Start date:
October 22, 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Swiss Group for Clinical Cancer Research
Agency class:
Other
Source:
Swiss Group for Clinical Cancer Research
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06401980
