Cabazitaxel in mCRPC Patients With AR-V7 Positive CTCs

NCT02621190 | Withdrawn Phase 2

• 1 other identifier: NL55865.078.15
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostatic Neoplasms

Keywords

circulating tumor cells; predictive factor

Outcome Measures

Primary Outcomes (1)

• Prostate specific antigen (PSA) response rate

  PSA response rate is defined as a reduction of at least 50% from baseline during therapy, confirmed after ≥4 weeks by an additional PSA evaluation.

  12 weeks after start of treatment

Secondary Outcomes (9)

• Circulating tumor cell (CTC) response rate

  9 weeks after start of treatment

• Prostate specific antigen (PSA) change from baseline

  12 weeks after start of treatment

• Maximum Prostate specific antigen (PSA) decrease

  through study completion, an average of two years

• Progression-free survival

  from date of treatment allocation until the date of first documented progression (see description) or date of death from any cause, whichever came first, assessed through study completion, up to 100 months

• Overall survival

  time from treatment group allocation to death due to any cause, assessed through study completion, up to 100 months

Study Arms (2)

A

NO INTERVENTION

patients without CTCs or AR-V7 negative CTCs are treated according to their physician's discretion

B

EXPERIMENTAL

patients with AR-V7 positive CTCs are treated with cabazitaxel 25mg/m2 q3w

Drug: cabazitaxel

Interventions

cabazitaxel DRUG

25mg/m2 q3w

Also known as: Jevtana

B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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)
• Abnormal hematological blood counts consisting of any of the following (within 21 days before treatment group allocation):

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Sanofi: collaborator

Study Sites (1)

Erasmus MC Cancer Institute

Rotterdam, 3075 EA, Netherlands

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplastic Cells, Circulating

Interventions

cabazitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: oncologist

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: December 3, 2015
• Study Start: February 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: June 1, 2019
• Last Updated: August 17, 2016

Record last verified: 2016-08

Locations

NL (1)