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

NCT02485691 | Completed Phase 4 Results

• 3 other identifiers: LPS142012014-004676-29U1111-1166-5329
• Study Type: interventional
• Target: 255
• Locations: 13 countries
• Sites: 65

Brief 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 participants who have been treated with docetaxel and who had disease progression while receiving AR-targeted therapy within 12 months of AR treatment initiation (less than or equal to \[\<=\]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.

Conditions

Prostate Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-Free Survival (rPFS)

  Radiographic progression-free survival: time (in months) from randomization to occurrence of any one of following: radiological tumor progressions using response evaluation criteria in solid tumors (RECIST 1.1), progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria or occurrence of death due to any cause. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Progression of bone lesions (PCWG2 criteria): first bone scan with \>= 2 new lesions compared to Baseline observed less than (\<) 12 weeks from randomization and confirmed by a second bone scan performed \>=6 weeks; first bone scan with \>=2 new lesions compared to Baseline observed \>=12 weeks from randomization. In accordance with protocol, data cut-off date for final analysis of this endpoint was the date when 196 rPFS events had occurred. Analysis done by Kaplan-Meier method.

  From randomization until tumor progression or bone lesion progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Secondary Outcomes (13)

• Overall Survival (OS)

  From randomization to death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

• Progression Free Survival (PFS)

  From randomization until tumor progression or bone lesion progression, pain progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

• Percentage of Participants With Prostate Specific Antigen (PSA) Response

  Baseline up to PSA response, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

• Percentage of Participants With Overall Objective Tumor Response

  From randomization until disease progression, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

• Time to PSA Progression (TTPP)

  From time from randomization until PSA progression, death due to any cause or data cut-off whichever comes first (maximum duration: up to 141 weeks)

Study Arms (2)

Cabazitaxel

EXPERIMENTAL

Participants received Cabazitaxel 25 mg/m\^2 intravenous (IV) infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic granulocyte-colony stimulating factor (G-CSF) as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).

Drug: cabazitaxel XRP6258; Drug: prednisone

Abiraterone acetate or enzalutamide

EXPERIMENTAL

Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).

Drug: enzalutamide; Drug: abiraterone acetate; Drug: prednisone

Interventions

cabazitaxel XRP6258 DRUG

Pharmaceutical form: solution Route of administration: intravenous

Also known as: Jevtana

Cabazitaxel

enzalutamide DRUG

Pharmaceutical form: capsule Route of administration: oral

Also known as: Xtandi

Abiraterone acetate or enzalutamide

abiraterone acetate DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Zytiga

Abiraterone acetate or enzalutamide

prednisone DRUG

Pharmaceutical form: tablet Route of administration: oral

Abiraterone acetate or enzalutamide; Cabazitaxel

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed prostate adenocarcinoma.
• Metastatic disease.
• Effective castration with serum testosterone levels less than (\<)0.5 ng/mL. If the participant has been treated with Luteinizing hormone-releasing hormone agonist (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 (RECIST 1.1 criteria).
• Appearance of 2 or more new bone lesions (PCWG2).
• Rising Prostate Specific Antigen (PSA) (PCWG2).
• Having received prior docetaxel for at least 3 cycles (before or after an AR-targeted therapy). Docetaxel administration in combination with androgen deprivation therapy (ADT) in metastatic hormone-sensitive disease was considered a prior exposure. Docetaxel rechallenge was 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 was longer than 12 months. Participants treated with Abiraterone Acetate + ADT in metastatic hormone-sensitive setting were eligible in the study if they have progressed within 12 months with the AR-targeted agent. Participants having PSA progression only (as per PCWG2) within 12 months were eligible.
• A PSA value of at least 2 ng/mL was 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.

You may not qualify if:

• 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.
• 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 were allowed, as well as any other cancer for which treatment has been completed \>=5 years ago and from which the participant 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.
• Participants 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 was based on respective study treatment labelling and country-specific regulatory requirements, and were 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;

Sponsors & Collaborators

• Sanofi: lead

Study Sites (65)

Investigational Site Number 040002

Linz, 4010, Austria

Location

Investigational Site Number 040003

Vienna, 1090, Austria

Location

Investigational Site Number 040004

Vienna, 1090, Austria

Location

Investigational Site Number 056013

Bruges, 8310, Belgium

Location

Investigational Site Number 056003

Brussels, 1000, Belgium

Location

Investigational Site Number 056007

Brussels, 1070, Belgium

Location

Investigational Site Number 056006

Charleroi, BE-6000, Belgium

Location

Investigational Site Number 056001

Ghent, 9000, Belgium

Location

Investigational Site Number 056005

Leuven, 3000, Belgium

Location

Investigational Site Number 203005

Brno, 65653, Czechia

Location

Investigational Site Number 203001

Olomouc, 77900, Czechia

Location

Investigational Site Number 203002

Pilsen, 30460, Czechia

Location

Investigational Site Number 203003

Prague, 14059, Czechia

Location

Investigational Site Number 250010

Clermont-Ferrand, 63011, France

Location

Investigational Site Number 250006

Lyon, 69373, France

Location

Investigational Site Number 250004

Marseille, 13273, France

Location

Investigational Site Number 250011

Montpellier, 34298, France

Location

Investigational Site Number 250013

Paris, 75005, France

Location

Investigational Site Number 250007

Paris, 75010, France

Location

Investigational Site Number 250002

Paris, 75015, France

Location

Investigational Site Number 250014

Plérin, 22190, France

Location

Investigational Site Number 250016

Reims, France

Location

Investigational Site Number 250018

Saint-Mandé, 94160, France

Location

Investigational Site Number 250009

Strasbourg, 67091, France

Location

Investigational Site Number 250005

Suresnes, 92150, France

Location

Investigational Site Number 250008

Tours, 37044, France

Location

Investigational Site Number 250001

Villejuif, 94800, France

Location

Investigational Site Number 276028

Aschaffenburg, 63739, Germany

Location

Investigational Site Number 276008

Berlin, 14179, Germany

Location

Investigational Site Number 276022

Duisburg, 47179, Germany

Location

Investigational Site Number 276023

Essen, 45136, Germany

Location

Investigational Site Number 276002

Frankfurt am Main, 60488, Germany

Location

Investigational Site Number 276007

Göttingen, 37075, Germany

Location

Investigational Site Number 276026

Jena, 07747, Germany

Location

Investigational Site Number 276025

Lübeck, 23538, Germany

Location

Investigational Site Number 276004

Magdeburg, 39120, Germany

Location

Investigational Site Number 276018

Mannheim, 68167, Germany

Location

Investigational Site Number 276006

Münster, 48149, Germany

Location

Investigational Site Number 276003

Nürtingen, 72622, Germany

Location

Investigational Site Number 276010

Rostock, 18107, Germany

Location

Investigational Site Number 276011

Tübingen, 72076, Germany

Location

Investigational Site Number 300001

Athens, 11528, Greece

Location

Investigational Site Number 300005

Marousi, Athens, 15125, Greece

Location

Investigational Site Number 300004

Thessaloniki, 56429, Greece

Location

Investigational Site Number 352001

Reykjavik, 101, Iceland

Location

Investigational Site Number 372001

Dublin, Ireland

Location

Investigational Site Number 372003

Dublin, Ireland

Location

Investigational Site Number 380004

Brescia, 25123, Italy

Location

Investigational Site Number 380005

Candiolo, Italy

Location

Investigational Site Number 380009

Meldola, Italy

Location

Investigational Site Number 380006

Napoli, Italy

Location

Investigational Site Number 380002

Pisa, Italy

Location

Investigational Site Number 380001

Roma, 00152, Italy

Location

Investigational Site Number 380008

Verona, Italy

Location

Investigational Site Number 528002

Breda, 4818CK, Netherlands

Location

Investigational Site Number 528003

Nijmegen, 6525GA, Netherlands

Location

Investigational Site Number 528005

Rotterdam, 3015GD, Netherlands

Location

Investigational Site Number 528004

Sittard-Geleen, 6162BG, Netherlands

Location

Investigational Site Number 578001

Grålum, 1714, Norway

Location

Investigational Site Number 578002

Trondheim, 7006, Norway

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Investigational Site Number 724004

Madrid, 28041, Spain

Location

Investigational Site Number 724002

Madrid, 28046, Spain

Location

Investigational Site Number 724003

Seville, 41013, Spain

Location

Investigational Site Number 826001

Sutton, SM25PT, United Kingdom

Location

Related Publications (5)

• Longoria O, Rekowski J, Gupta S, Beije N, Pantel K, Efstathiou E, Sternberg C, Castellano D, Fizazi K, Tombal B, Sharp A, Sartor O, Mace S, Geffriaud-Ricouard C, Wenstrup R, de Wit R, de Bono J. Chromosomal instability in circulating tumor cells and cabazitaxel resistance in metastatic castration-resistant prostate cancer. JCI Insight. 2025 Nov 4;10(24):e196505. doi: 10.1172/jci.insight.196505. eCollection 2025 Dec 22.

  PMID: 41186991 DERIVED

• de Wit R, Wulfing C, Castellano D, Kramer G, Eymard JC, Sternberg CN, Fizazi K, Tombal B, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Foster MC, Ozatilgan A, Geffriaud-Ricouard C, de Bono J. Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study. ESMO Open. 2021 Oct;6(5):100241. doi: 10.1016/j.esmoop.2021.100241. Epub 2021 Aug 24.

  PMID: 34450475 DERIVED

• Sternberg CN, Castellano D, de Bono J, Fizazi K, Tombal B, Wulfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, de Wit R. Efficacy and Safety of Cabazitaxel Versus Abiraterone or Enzalutamide in Older Patients with Metastatic Castration-resistant Prostate Cancer in the CARD Study. Eur Urol. 2021 Oct;80(4):497-506. doi: 10.1016/j.eururo.2021.06.021. Epub 2021 Jul 15.

  PMID: 34274136 DERIVED

• Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wulfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. doi: 10.1016/S1470-2045(20)30449-6. Epub 2020 Sep 11.

  PMID: 32926841 DERIVED

• de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. doi: 10.1056/NEJMoa1911206. Epub 2019 Sep 30.

  PMID: 31566937 DERIVED

MeSH Terms

Interventions

cabazitaxel; enzalutamide; Abiraterone Acetate; Prednisone

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: June 30, 2015
• Study Start: November 9, 2015
• Primary Completion: March 27, 2019
• Study Completion: March 15, 2021
• Last Updated: May 27, 2022
• Results First Posted: February 14, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

BE (6); IE (2); CZ (4); AU (3); NL (4); ES (4); NO (2); GB (1); GR (3); IT (7); FR (14); DE (14); IC (1)