metastatic castration-resistant prostate cancer
Conditions
Interventions
Trade Name: Cabazitaxel
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • 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) • Concomitant vaccination with yellow fever vaccine • Abnormal liver functions consisting of any of the following (within 21 XML File Identifier: Ox6Q0W5xu5l8id6EpdbT1nRYoE4= Page 11/21 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Explore the PSA response rate to cabazitaxel in mCRPC patients who have progressed to docetaxel and have detectable AR-V7 expression in CTCs;Secondary Objective: PSA response to third-line cabazitaxel after enzalutamide or abiraterone treatment, toxicity of cabazitaxel in second and third-line treatment, as well as cabazitaxel pharmacokinetics in relation to response. We will explore associations between other AR splice variants and response to cabazitaxel treatment. We will also explore differences in AR splice variant expression before and after therapy, to gain insight into possible mechanisms of resistance and means to predict treatment resistance at an early time point. In addition, we will analyze cfDNA for dynamic changes during treatment and tumor-specific mutations.;Primary end point(s): PSA response rate, defined as the percentage of AR-V7 positive cabazitaxel-treated patients with a =50% PSA decline from baseline.;Timepoint(s) of evaluation of this end point: 12-15 weeks after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CTC response rate, progression-free survival and overall survival to cabazitaxel in AR-V7 positive patients, as well as toxicity and cumulative administered dose of cabazitaxel in second and third-line therapy. Furthermore, we want to explore the relationship between systemic cabazitaxel exposure and response;Timepoint(s) of evaluation of this end point: PFS, OS, toxicity and cumulative administered cabazitaxel dose: end of the study CTC response rate, relation between response and systemic cabazitaxel exposure: 12-15 weeks after start of the study | — |
Countries
Netherlands
Contacts
Public ContactClinical Trial Center
Erasmus MC cancer institute
Outcome results
None listed