Overview

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Withdrawn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