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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 (CARD)

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ClinicalTrials.gov Identifier: NCT02485691
Recruitment Status : Active, not recruiting
First Posted : June 30, 2015
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

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 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: cabazitaxel XRP6258 Drug: enzalutamide Drug: abiraterone acetate Drug: prednisone Phase 4

Detailed Description:
The duration of the study per patient will be approximately 2 years. Each patient will be treated until radiographic disease progression, unacceptable toxicity, or patient's refusal of further study treatment, and each patient will be followed after completion of study treatment until death, study cutoff date, or withdrawal of patient consent.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 324 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : November 9, 2015
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: Cabazitaxel
Cabazitaxel 25 mg/m^2 intravenously in 1 hour every 3 weeks + prednisone 10 mg orally given daily + Primary prophylactic G-CSF (the choice of the G-CSF product is left to the Investigator's decision). Treatment will continue until confirmed disease progression or unacceptable toxicity.
Drug: cabazitaxel XRP6258
Pharmaceutical form:solution Route of administration: intravenous
Other Name: Jevtana

Drug: prednisone
Pharmaceutical form:tablet Route of administration: oral

Experimental: Abiraterone acetate or enzalutamide
Abiraterone acetate oral 1000 mg once daily continuously + prednisone 5 mg orally given twice daily OR enzalutamide oral 160 mg once daily continuously. Treatment will continue until confirmed disease progression or unacceptable toxicity.
Drug: enzalutamide
Pharmaceutical form:capsule Route of administration: oral
Other Name: Xtandi

Drug: abiraterone acetate
Pharmaceutical form:tablet Route of administration: oral
Other Name: Zytiga

Drug: prednisone
Pharmaceutical form:tablet Route of administration: oral




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. Number of patients achieving PSA decline >=50% [ Time Frame: Up to 2 years ]
  2. Progression-free survival-Time [ Time Frame: Up to 2 years ]
  3. 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 ]
  4. 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 ]
  5. Number of patients achieving tumor response [ Time Frame: Up to 2 years ]
  6. Duration of tumor response [ Time Frame: Up to 2 years ]
  7. Pain response using Brief Pain Inventory-Short Form (BPI-SF) for pain intensity score [ Time Frame: Up to 2 years ]
  8. Time to pain progression [ Time Frame: Up to 2 years ]
  9. Symptomatic skeletal event (SSE) rate [ Time Frame: Up to 2 years ]
  10. 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 ]
  11. Assessment of health status using the 5-Level EuroQol Group's 5-Dimension (EQ-5D-5L) questionnaire [ Time Frame: Up to 2 years ]
  12. Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 30 days after the last treatment administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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, or intra uterine device or will be based on country-specific regulatory requirements, and 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02485691


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

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02485691     History of Changes
Other Study ID Numbers: LPS14201
2014-004676-29 ( EudraCT Number )
U1111-1166-5329 ( Other Identifier: UTN )
First Posted: June 30, 2015    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Abiraterone Acetate
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors