This study has been transitioned to CTIS with ID 2024-516939-28-00 check the CTIS register for the current data. To compare progression free survival (PFS) between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is progression free survival, which is defined as time
from randomization to radiologic, biochemical or pain progression or death from
any cause, whichever occurs first, according to PCWG3
Secondary outcome
1. Overall survival, defined as time from randomization to death from any cause.
2. Time to progression, defined as time from randomization to radiologic,
biochemical or pain progression, whichever occurs first.
3. The time to PSA progression, defined as time from randomization to
biochemical progression.
4. The time to pain progression, defined as time from randomization to pain
progression.
5. The number and severity of adverse events
6. Cell-free DNA aneuploidy scores and somatic aberrations in circulating tumor
DNA
7. CTC-count.
8. Differential expression of relevant genes.
Background summary
Taxane efficacy in metastatic prostate cancer is limited due to resistance
development. Several clinical phase III studies in metastatic castration-naïve
prostate cancer (mCNPC) patients have shown that adding an androgen receptor
signalling inhibitor (ARSi) to patients receiving a taxane and androgen
deprivation therapy (ADT) improves survival endpoints. Adding ARSi darolutamide
to docetaxel+ADT in mCNPC patients resulted in a robust OS benefit (HR 0.68).
Importantly, the combination of a taxane and darolutamide is not prone to a
drug-drug interaction, while there is a detrimental CYP3A4 inducing effect in
the case of enzalutamide, resulting in a significant and clinically relevant
reduction of cabazitaxel plasma concentrations. We have previously reported
preclinical data showing that addition of an androgen receptor signaling
inhibitor (ARSi) improves cabazitaxel efficacy, even in metastatic
castration-resistant prostate cancer (mCRPC). As treatment options for mCRPC
patients are scarce and patients often develop drug resistance relatively
early, a new treatment regimen for this population to delay drug resistance is
highly desired. We propose a randomized phase II trial to investigate the
efficacy of docetaxel or cabazitaxel plus darolutamide compared to docetaxel or
cabazitaxel monotherapy in men with metastatic CRPC, who have progressed on an
ARSI.
Study objective
This study has been transitioned to CTIS with ID 2024-516939-28-00 check the CTIS register for the current data.
To compare progression free survival (PFS) between treatment with docetaxel or
cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in
mCRPC patients.
Study design
This is a randomized phase II trial.
Intervention
Before starting their taxane regimen, patients will be randomized 1 : 1 to
receive darolutamide (600 mg b.i.d.) or not, until the end of their final
taxane treatment cycle. Radiological follow-up will be according to standard of
care. In addition, patients will undergo extra blood drawings at a maximum of 4
timepoints (baseline, after 3 and 6 cycles and at progression) for ctDNA and
circulating tumour cell (CTC) analysis. Furthermore, a small subset of patients
(n=25) will undergo a tissue biopsy twice and 40 patients will undergo
diagnostic leukapheresis (DLA) for enrichment of CTCs for further molecular
analysis.
Study burden and risks
Patients in the darolutamide group, will receive darolutamide 600 mg b.i.d.
during taxane treatment, in addition to current standard of care treatment.
Major risks to be expected are side effects of darolutamide treatment. All
patients will undergo extra blood drawings at a maximum of 4 timepoints and a
subset will undergo DLA twice. Tissue biopsies will be performed in a small
subset of patients. Standard complications of tissue biopsies are the relevant
risk for these patients.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 18 years;
2. A confirmed diagnosis of progressive mCRPC (progression according to
Prostate cancer Working Group (PCWG) 3 criteria), with an indication for
docetaxel or cabazitaxel. Progression defined as >= 1 of the following 3
criteria:
a. Radiographic disease progression in soft tissue per RECIST v1.1
b. Radiographic disease progression in bone defined by the appearance of >= 2
new bone lesions on bone scan.
c. PSA progression defined as >= 2 sequential rises in PSA obtained >= 1 week
apart with a minimal starting value of >= 1 ng/mL. A PSA value >= 2 ng/mL is
required at study entry.
3. Patients should have had disease progression previously on at least one ARSi
(abiraterone, apalutamide, darolutamide or enzalutamide). ARSi administration
is allowed both in the mCNPC and in the mCRPC setting. Co-administration of
docetaxel in mCNPC (triplet-therapy) is allowed.
4. WHO performance <= 2 (see appendix A)
5. Able and willing to sign the Informed Consent Form prior to screening
evaluations
6. Adequate haematological, renal and liver function and chemistry, defined as:
a. Hemoglobin >= 6.0 mmol/L
b. Platelets >= 100 x 109/L
c. ALT/AST <= 3x ULN and <= 5x ULN in case of liver metastases
d. Creatinine clearance >= 50 ml/min
e. Serum testosterone <= 1.7 nmol/L
Exclusion criteria
1. Impossibility or unwillingness to take oral drugs
2. Hypersensitivity to taxanes
3. Known serious illness or medical unstable conditions that could interfere
with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or
herpes zoster, organ transplants, kidney failure, serious liver disease (e.g.
severe cirrhosis), cardiac and respiratory diseases)
4. Symptomatic peripheral neuropathy CTCAE grade >=2
5. Docetaxel-rechallenge.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-516939-28-00 |
| EudraCT | EUCTR2022-003792-41-NL |
| CCMO | NL83539.078.23 |