A randomized phase II trial of docetaxel or cabazitaxel with or without darolutamide in men with metastatic castration-resistant prostate cancer.
- Conditions
- Metastatic castration-resistant prostate cancermetastatic prostate cancer10038597
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 245
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
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The main study endpoint is progression free survival, which is defined as time<br /><br>from randomization to radiologic, biochemical or pain progression or death from<br /><br>any cause, whichever occurs first, according to PCWG3 </p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Overall survival, defined as time from randomization to death from any cause.<br /><br>2. Time to progression, defined as time from randomization to radiologic,<br /><br>biochemical or pain progression, whichever occurs first.<br /><br>3. The time to PSA progression, defined as time from randomization to<br /><br>biochemical progression.<br /><br>4. The time to pain progression, defined as time from randomization to pain<br /><br>progression.<br /><br>5. The number and severity of adverse events<br /><br>6. Cell-free DNA aneuploidy scores and somatic aberrations in circulating tumor<br /><br>DNA<br /><br>7. CTC-count.<br /><br>8. Differential expression of relevant genes.</p><br>