A Randomized, Open Label, Multicenter Study of Cabazitaxel Versus an Androgen Receptor (AR)-Targeted Agent (Abiraterone or Enzalutamide) in mCRPC Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)

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A Randomized, Open Label, Multicenter Study of Cabazitaxel Versus an Androgen Receptor (AR)-Targeted Agent (Abiraterone or Enzalutamide) in mCRPC Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)

Condition: Prostate Cancer Metastatic

Intervention:

  • Drug: cabazitaxel XRP6258
  • Drug: enzalutamide
  • Drug: abiraterone acetate
  • Drug: prednisone

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02485691

Sponsor: Sanofi

Primary Outcome Measures:

  • Measure: Radiographic progression-free survival defined as the time from randomization to the occurrence of radiological tumor progressions using RECIST 1.1 and progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Radiographic progression-free survival defined as the time from randomization to the occurrence of death due to any cause
  • Time Frame: Up to 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of patients achieving PSA decline >=50%
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Progression-free survival-Time
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Overall survival defined as the time interval from the date of randomization to the date of death due to any cause
  • Time Frame: Up to 2 years posttreatment
  • Safety Issue:
  • Measure: Time to Prostate Specific Antigen (PSA) progression defined as the time interval between the date of randomization and the date of PSA progression using PCWG2 definition
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Number of patients achieving tumor response
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Duration of tumor response
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pain response using Brief Pain Inventory-Short Form (BPI-SF) for pain intensity score
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Time to pain progression
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Symptomatic skeletal event (SSE) rate
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Assessment of Health-related Quality of Life (HRQOL) using the Functional Assessment of Cancer Therapy – Prostate (FACT-P) scale
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Assessment of health status using the 5-Level EuroQol Group’s 5-Dimension (EQ-5D-5L) questionnaire
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Number of treatment-emergent adverse events (TEAEs)
  • Time Frame: Up to 30 days after the last treatment administration
  • Safety Issue:

Estimated Enrollment: 234

Study Start Date: November 9, 2015

Phase: Phase 4

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Histologically confirmed prostate adenocarcinoma.
  • Metastatic disease.
  • Effective castration with serum testosterone levels
  • 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
  • Absolute neutrophil count
  • Platelet count
  • 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
  • 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.

Locations:

  • Investigational Site Number 040002
  • Linz 4010 Austria
  • Investigational Site Number 040003
  • Wien 1090 Austria
  • Investigational Site Number 040004
  • Wien 1090 Austria
  • Investigational Site Number 056013
  • Brugge 8310 Belgium
  • Investigational Site Number 056011
  • Brugge B-8000 Belgium
  • Investigational Site Number 056007
  • Brussels 1070 Belgium
  • Investigational Site Number 056003
  • Bruxelles 1000 Belgium
  • Investigational Site Number 056002
  • Bruxelles 1200 Belgium
  • Investigational Site Number 056006
  • Charleroi BE-6000 Belgium
  • Investigational Site Number 056001
  • Gent 9000 Belgium
  • Investigational Site Number 056005
  • Leuven 3000 Belgium
  • Investigational Site Number 056010
  • Roeselare 8800 Belgium
  • Investigational Site Number 056008
  • Turnhout 2300 Belgium
  • Investigational Site Number 203005
  • Brno 65653 Czechia
  • Investigational Site Number 203001
  • Olomouc 77900 Czechia
  • Investigational Site Number 203002
  • Plzen 30460 Czechia
  • Investigational Site Number 203003
  • Praha 4 14059 Czechia
  • Investigational Site Number 250012
  • Besancon 25030 France
  • Investigational Site Number 250010
  • Clermont Ferrand 63011 France
  • Investigational Site Number 250006
  • LYON Cedex 8 69373 France
  • Investigational Site Number 250019
  • Lyon 69009 France
  • Investigational Site Number 250004
  • Marseille 13273 France
  • Investigational Site Number 250011
  • Montpellier 34298 France
  • Investigational Site Number 250002
  • PARIS Cedex 15 75015 France
  • Investigational Site Number 250013
  • Paris 75005 France
  • Investigational Site Number 250007
  • Paris 75010 France
  • Investigational Site Number 250014
  • Plerin 22190 France
  • Investigational Site Number 250016
  • Reims France
  • Investigational Site Number 250018
  • Saint-Mandé 94160 France
  • Investigational Site Number 250009
  • Strasbourg 67091 France
  • Investigational Site Number 250005
  • Suresnes 92150 France
  • Investigational Site Number 250008
  • Tours 37044 France
  • Investigational Site Number 250001
  • Villejuif 94800 France
  • Investigational Site Number 276028
  • Aschaffenburg 63739 Germany
  • Investigational Site Number 276027
  • Berlin 10967 Germany
  • Investigational Site Number 276008
  • Berlin 14179 Germany
  • Investigational Site Number 276022
  • Duisburg 47179 Germany
  • Investigational Site Number 276013
  • Düsseldorf 40225 Germany
  • Investigational Site Number 276016
  • Erlangen 91054 Germany
  • Investigational Site Number 276023
  • Essen 45136 Germany
  • Investigational Site Number 276002
  • Frankfurt am Main 60488 Germany
  • Investigational Site Number 276007
  • Göttingen 37075 Germany
  • Investigational Site Number 276009
  • Hamburg 20246 Germany
  • Investigational Site Number 276001
  • Hamburg 22763 Germany
  • Investigational Site Number 276017
  • Homburg/Saar 66421 Germany
  • Investigational Site Number 276026
  • Jena 07747 Germany
  • Investigational Site Number 276012
  • Köln 50968 Germany
  • Investigational Site Number 276025
  • Lübeck 23538 Germany
  • Investigational Site Number 276004
  • Magdeburg 39120 Germany
  • Investigational Site Number 276019
  • Mainz 55131 Germany
  • Investigational Site Number 276018
  • Mannheim 68167 Germany
  • Investigational Site Number 276006
  • Münster 48149 Germany
  • Investigational Site Number 276003
  • Nürtingen 72622 Germany
  • Investigational Site Number 276010
  • Rostock 18107 Germany
  • Investigational Site Number 276024
  • Stuttgart 70176 Germany
  • Investigational Site Number 276011
  • Tübingen 72076 Germany
  • Investigational Site Number 276020
  • Wuppertal 42103 Germany
  • Investigational Site Number 300001
  • Athens 11528 Greece
  • Investigational Site Number 300002
  • Athens 15562 Greece
  • Investigational Site Number 300005
  • Marousi, Athens 15125 Greece
  • Investigational Site Number 300004
  • Thessaloniki 56429 Greece
  • Investigational Site Number 352001
  • Reykjavik 101 Iceland
  • Investigational Site Number 372001
  • Dublin 24 Ireland
  • Investigational Site Number 372003
  • Dublin 7 Ireland
  • Investigational Site Number 372004
  • Dublin D7 Ireland
  • Investigational Site Number 380003
  • Arezzo 06156 Italy
  • Investigational Site Number 380004
  • Brescia 25123 Italy
  • Investigational Site Number 380005
  • Candiolo Italy
  • Investigational Site Number 380009
  • Meldola Italy
  • Investigational Site Number 380007
  • Napoli 80131 Italy
  • Investigational Site Number 380006
  • Napoli Italy
  • Investigational Site Number 380011
  • Parma 43100 Italy
  • Investigational Site Number 380002
  • Pisa Italy
  • Investigational Site Number 380001
  • Roma 00152 Italy
  • Investigational Site Number 380008
  • Verona Italy
  • Investigational Site Number 528002
  • Breda 4818CK Netherlands
  • Investigational Site Number 528007
  • Enschede 7545KZ Netherlands
  • Investigational Site Number 528003
  • Nijmegen 6525GA Netherlands
  • Investigational Site Number 528005
  • Rotterdam 3015GD Netherlands
  • Investigational Site Number 528004
  • Sittard-Geleen 6162BG Netherlands
  • Investigational Site Number 578001
  • Grålum 1714 Norway
  • Investigational Site Number 578002
  • Trondheim 7006 Norway
  • Investigational Site Number 724001
  • Barcelona 08035 Spain
  • Investigational Site Number 724004
  • Madrid 28041 Spain
  • Investigational Site Number 724002
  • Madrid 28046 Spain
  • Investigational Site Number 724003
  • Sevilla 41013 Spain
  • Investigational Site Number 826001
  • Sutton SM25PT United Kingdom

View trial on ClinicalTrials.gov

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