Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

Tracking Information
First Submitted Date  ICMJE June 26, 2015
First Posted Date  ICMJE June 30, 2015
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE November 9, 2015
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2018)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2015)
  • Radiographic progression-free survival defined as the time from randomization to the occurrence of radiological tumor progressions using RECIST 1.1 and PCWG2 criteria [ Time Frame: Up to 2 years ]
  • 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 ]
Change History Complete list of historical versions of study NCT02485691 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2018)
  • Number of patients achieving PSA decline >=50% [ Time Frame: Up to 2 years ]
  • Progression-free survival-Time [ Time Frame: Up to 2 years ]
  • 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 ]
  • 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 ]
  • Number of patients achieving tumor response [ Time Frame: Up to 2 years ]
  • Duration of tumor response [ Time Frame: Up to 2 years ]
  • Pain response using Brief Pain Inventory-Short Form (BPI-SF) for pain intensity score [ Time Frame: Up to 2 years ]
  • Time to pain progression [ Time Frame: Up to 2 years ]
  • Symptomatic skeletal event (SSE) rate [ Time Frame: Up to 2 years ]
  • 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 ]
  • Assessment of health status using the 5-Level EuroQol Group's 5-Dimension (EQ-5D-5L) questionnaire [ Time Frame: Up to 2 years ]
  • Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 30 days after the last treatment administration ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2015)
  • Number of patients achieving PSA decline >=50% [ Time Frame: Up to 2 years ]
  • Progression-free survival-Time [ Time Frame: Up to 2 years ]
  • 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 ]
  • Time to 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 ]
  • Number of patients achieving tumor response [ Time Frame: Up to 2 years ]
  • Duration of tumor response [ Time Frame: Up to 2 years ]
  • Pain response using Brief Pain Inventory-Short Form (BPI-SF) for pain intensity score [ Time Frame: Up to 2 years ]
  • Time to pain progression [ Time Frame: Up to 2 years ]
  • Symptomatic skeletal event (SSE) rate [ Time Frame: Up to 2 years ]
  • Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 30 days after the last treatment administration ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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)
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.
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.
Study Type  ICMJE Interventional
Study Phase Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer Metastatic
Intervention  ICMJE
  • Drug: cabazitaxel XRP6258
    Pharmaceutical form:solution Route of administration: intravenous
    Other Name: Jevtana
  • 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
Study Arms
  • 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.
    Interventions:
    • Drug: cabazitaxel XRP6258
    • Drug: prednisone
  • 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.
    Interventions:
    • Drug: enzalutamide
    • Drug: abiraterone acetate
    • Drug: prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
324
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2015)
274
Estimated Study Completion Date August 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Czechia,   France,   Germany,   Greece,   Iceland,   Ireland,   Italy,   Netherlands,   Norway,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02485691
Other Study ID Numbers  ICMJE LPS14201
2014-004676-29 ( EudraCT Number )
U1111-1166-5329 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP