Cabazitaxel in mCRPC Patients With AR-V7 Positive CTCs

• Status: Withdrawn
• Trial end date: 2019-06-01
• Target enrollment: 0
• Participant gender: Male

Summary

After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available. In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center
• Collaborator: Sanofi

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 <50 ng/mL (1.7 nmol/L) within 21 days before treatment group allocation.

• Age ≥18 years

• Disease progression during or after treatment with docetaxel. Disease progression for study entry is defined as one or more of the following criteria:

• PSA progression defined by at least 2 consecutive PSA rises over a reference value, with an interval of ≥ 1 week between each determination. PSA at screening visit should be ≥ 2.0 μg/l.

• Bone disease progression defined by the appearance of new lesions on a bone scan, confirmed on a second bone scan ≥ 6 weeks later.

• Soft tissue disease progression defined by modified RECIST criteria 1.1 (baseline LN size must be ≥ 2.0 cm to be considered target or evaluable lesion) (15)

• ECOG performance status 0-2 (appendix A)

• Written informed consent according to ICH-GCP before study treatment and any study specific procedures

Exclusion Criteria:

• Impossibility or unwillingness to take oral drugs

• 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 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