A single arm phase 2 multicenter study determining the response to Cabazitaxel in metastatic prostate cancer (mCRPC) patients with AR-V7 positive circulating tumor cells (CTCs)
- Conditions
- metastatic castration-resistant prostate cancermetastatic hormone-refractory prostate cancer10038597
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 125
Histologically or cytologically confirmed adenocarcinoma of the prostate
without neuroendocrine differentiation or small cell features.
- Continued androgen deprivation therapy either by LHRH
agonists/antagonists or orchiectomy.
- Serum testosterone <50 ng/ml (1.7 nmol/L) within 21 days of
treatment start (if patient enters treatment phase of the study)
- Age *18 years
progression for study entry is defined as one or more of the following
criteria:
* At least 3 consecutive PSA rises over a reference value, with an
interval of * 1 week between each determination. PSA at screening visit
should be * 2.0 *g/l.
* Bone disease progression defined by the appearance of *2 new
lesions on a bone scan (confirmed by a second bone scan 6 weeks later).
* Soft tissue disease progression defined by modified RECIST 1.1.
- ECOG performance status 0-2
- Written informed consent according to ICH-GCP
* Geographical, psychological or other non-medical conditions interfering with follow-up
* Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection)
* Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
* Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion.
* Prior treatment with cabazitaxel
* Successive treatment with both abiraterone and enzalutamide in the post-docetaxel setting
* Radiotherapy to 40% or more of the bone marrow
* Known hypersensitivity to corticosteroids
* History of severe hypersensitivity reaction (*grade 3) to docetaxel
* History of severe hypersensitivity reaction (*grade 3) to polysorbate 80 containing drugs
* Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix C of protocol)
* Concomitant vaccination with yellow fever vaccine
* Abnormal liver functions consisting of any of the following (within 21 days before treatment group allocation):
* Total bilirubin > 1.5 x ULN (except for patients with documented Gilbert's disease)
* If total bilirubin > 1 x ULN or AST > 1.5 x ULN inclusion is permitted but cabazitaxel dose should be reduced 20mg/m2
* Abnormal hematological blood counts consisting of any of the following (within 21 days before treatment group allocation):
* Absolute neutrophil count < 1.5 x 109/L
* Platelets < 100 x 109/L
* Hemoglobin < 6.2 mmol/L
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is PSA response, defined as a *50% PSA decline from<br /><br>baseline during therapy. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints include CTC response, progression-free survival and overall<br /><br>survival to cabazitaxel in AR-V7 positive patients, as well as toxicity and<br /><br>cumulative administered dose of cabazitaxel in second and third-line therapy.<br /><br>Furthermore, we want to explore the relationship between systemic cabazitaxel<br /><br>exposure and response.</p><br>