Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent

• Status: Completed
• Trial end date: 2021-03-15
• Target enrollment: 0
• Participant gender: Male

Summary

Primary Objective:

To compare the radiographic progression-free survival (rPFS) [using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for tumor lesions and Prostate Cancer Working Group 2 (PCWG2) criteria for bone scan lesions or death due to any cause] with chemotherapy (cabazitaxel plus prednisone, Arm A) versus Androgen Receptor (AR)-targeted therapy (enzalutamide or abiraterone acetate plus prednisone, Arm B) in mCRPC patients who have been treated with docetaxel and who had disease progression while receiving AR-targeted therapy within 12 months of AR treatment initiation (≤12 months, either before or after docetaxel).

Secondary Objective:

• To compare efficacy for:

• Prostate-specific antigen (PSA) response rate and time to PSA progression (TTPP).

• Progression-free survival (PFS).

• Overall survival (OS).

• Tumor response rate and duration of tumor response.

• Pain response and time to pain progression.

• Symptomatic skeletal event (SSE) rate and time to occurrence of any SSE.

• Health status and Health-related Quality of Life (HRQOL).

• To evaluate the correlation of a signature of resistance to AR-targeted agents with clinical outcome via the analysis of circulating tumor cell (CTC) phenotypes as well as expression and localization of proteins including AR isoforms in CTCs.

• To evaluate safety in the 2 treatment arms.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Abiraterone Acetate; Docetaxel; Prednisone

Criteria

Inclusion criteria :

Histologically confirmed prostate adenocarcinoma.

• Metastatic disease.

• Effective castration with serum testosterone levels <0.5 ng/mL. If the patient has been treated with LHRH agonists or antagonist (i.e., without orchiectomy), then this therapy should be continued.

• Progressive disease defined by at least one of the following:

• Progression in measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).

• Appearance of 2 or more new bone lesions (Prostate Cancer Working Group 2 [PCWG2]).

• Rising Prostate Specific Antigen (PSA) (PCWG2).

• Having received prior docetaxel for at least 3 cycles (before or after an Androgen Receptor (AR)-targeted therapy). Docetaxel administration in combination with androgen deprivation therapy (ADT) in metastatic hormone-sensitive disease is considered a prior exposure. Docetaxel rechallenge is allowed.

• Having progressive disease (PD) while receiving AR-targeted therapy with abiraterone acetate or enzalutamide within 12 months of AR treatment initiation (≤12 months), even if treatment duration is longer than 12 months. Patients treated with Abiraterone Acetate + ADT in metastatic hormone-sensitive setting are eligible in the study if they have progressed within 12 months with the AR-targeted agent. Patients having PSA progression only (as per PCWG2) within 12 months are eligible.

• A PSA value of at least 2 ng/mL is required at study entry.

• Prior AR-targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.

• Signed informed consent.

Exclusion criteria:

• Prior chemotherapy other than docetaxel for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago.

• Less than 28 days elapsed from prior treatment with chemotherapy, immunotherapy, radiotherapy, or surgery to the time of randomization.

• Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of Grade >1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.0) at the time of randomization.

• Eastern Cooperative Oncology Group performance status (ECOG PS) >2 (ECOG 2 must be related to prostate cancer, not to other comorbidities).

• Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which treatment has been completed ≥5 years ago and from which the patient has been disease-free for ≥5 years.

• Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.

• Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.

• Patients with reproductive potential who do not agree, in conjunction with their partner, to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose. The definition of "effective method of contraception" described hereafter: oral contraceptives, combined hormonal intravaginal, transdermal, intra uterine device or condoms will be based on respective study treatment labelling and country-specific regulatory requirements, and are documented in the Informed Consent Form.

• Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate, enzalutamide, docetaxel, or polysorbate 80.

• Known history of mineralocorticoid excess or deficiency.

• History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation, brain metastases, or the use of concomitant medications that may lower the seizure threshold.

• Unable to swallow a whole tablet or capsule.

• Inadequate organ and bone marrow function as evidenced by:

• Hemoglobin <10.0 g/dL;

• Absolute neutrophil count <1.5 × 10^9/L;

• Platelet count <100 × 10^9/L;

• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase and/or alanine aminotransferase/serum glutamic pyruvic transaminase >1.5 × the upper limit of normal (ULN);

• Total bilirubin >1.0 × ULN;

• Potassium <3.5 mmol/L;

• Child-Pugh Class C.

• Contraindications to the use of corticosteroid treatment.

• Symptomatic peripheral neuropathy Grade ≥2 (NCI CTCAE v4.0).

• Uncontrolled severe illness or medical condition including uncontrolled diabetes mellitus, history of cardiovascular disease (uncontrolled hypertension, arterial thrombotic events in the past 6 months, congestive heart failure, severe or unstable angina pectoris, recent myocardial infarction within the last 6 months, or uncontrolled cardiac arrhythmia).

• Concomitant vaccination with yellow fever vaccine.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.