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Cabazitaxel Versus the Switch to Alternative AR Targeted Therapy Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Primary Resistant Patients to Abiraterone or Enzalutamide (PRIMCAB)

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. Identifier: NCT02379390
Recruitment Status : Completed
First Posted : March 4, 2015
Last Update Posted : May 23, 2018
Information provided by (Responsible Party):

Brief Summary:

Primary Objective:

To demonstrate the superiority in term of radiographic Progression-Free Survival (rPFS) of cabazitaxel versus either enzalutamide or abiraterone plus prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) who have disease progression while receiving AR targeted therapy (abiraterone plus prednisone or enzalutamide) within 12 months of treatment initiation (≤12 months).

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 events (SSE) rate and time to occurrence of any SSE.
  • To analyze messenger ribonucleic acids (mRNAs) including androgen-receptor splice variant 7 messenger RNA (AR-V7) as a biomarker in Circulating Tumor Cells (CTCs).
  • To evaluate safety in the 2 treatment arms.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: Cabazitaxel XRP6258 Drug: Ezalutamide Drug: Abiraterone acetate Drug: Prednisone Phase 2

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)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II, Randomized, Open-label, Multicenter Study in Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Who Have PRIMary Resistance to Abiraterone Acetate or Enzalutamide Treatment Comparing the Anti-tumor Effect of CABazitaxel to Alternative Androgen Receptors (AR) Targeted Therapy
Study Start Date : June 17, 2015
Actual Primary Completion Date : May 10, 2018
Actual Study Completion Date : May 10, 2018

Arm Intervention/treatment
Experimental: Cabazitaxel
Cabazitaxel 25 mg/m^2 intravenously in 1 hour every three weeks + prednisone 10 mg orally given daily. Treatment will continue until confirmed disease progression or unacceptable toxicity
Drug: Cabazitaxel XRP6258
Other Name: Jevtana

Drug: Prednisone
Active Comparator: Abiraterone acetate or Enzalutamide
Abiraterone acetate 1000 mg orally, once daily + prednisone 5 mg orally given twice daily OR Enzalutamide 160 mg orally, once daily. Treatment will continue until confirmed disease progression or unacceptable toxicity
Drug: Ezalutamide
Other Name: Xtandi

Drug: Abiraterone acetate
Other Name: Zytiga

Drug: Prednisone

Primary Outcome Measures :
  1. Radiographic Progression-Free Survival (rPFS) defined as the time from randomization to the occurrence of radiological tumor progressions using RECIST 1.1 and PCWG2 criteria [ Time Frame: Up to 30 months ]
  2. Radiographic Progression-Free Survival (rPFS) defined as the time from randomization to the occurrence of death due to any cause [ Time Frame: Up to 30 months ]

Secondary Outcome Measures :
  1. Number of patients achieving PSA decline >=50% [ Time Frame: Up to 30 months ]
  2. Progression-free survival-Time [ Time Frame: Up to 30 months ]
  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 30 months posttreatment ]
  4. 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 30 months ]
  5. Number of patients achieving tumor response [ Time Frame: Up to 30 months ]
  6. Duration of tumor response [ Time Frame: Up to 30 months ]
  7. Pain response using Brief Pain Inventory-Short Form (BPI-SF) for pain intensity score [ Time Frame: Up to 30 months ]
  8. Time to pain progression [ Time Frame: Up to 30 months ]
  9. Number of patients with symptomatic skeletal event (SSE) [ Time Frame: Up to 30 months ]
  10. Number of patients with treatment-emergent adverse events (TEAE) [ 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

Inclusion criteria:

  • Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.
  • Metastatic disease.
  • Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide within 12 months of treatment initiation (≤12 months) by at least one of the following:
  • Progression in measurable disease Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2).
  • Rising PSA defined (PCWG2).
  • A PSA value of at least 2 ng/mL is required at study entry.
  • Effective castration (serum testosterone levels ≤0.5 ng/mL).
  • Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.
  • Signed written informed consent.

Exclusion criteria:

  • Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion. Prior docetaxel in hormone sensitive setting is allowed if completed >1 year before randomization. Prior immunotherapy is allowed.
  • Less than 28 days elapsed from prior treatment with 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 for Adverse Events [NCI CTCAE] v4.0) at the time of randomization.
  • Eastern Cooperative Oncology Group (ECOG) performance status >1.
  • History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
  • 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.
  • Any severe acute or chronic medical condition including uncontrolled diabetes mellitus, severe renal impairment, history of cardiovascular disease (uncontrolled hypertension, arterial thrombotic events in the past 6 months, congestive heart failure, severe or unstable angina pectoris, recent myocardial infraction within last 6 months or uncontrolled cardiac arrhythmia), which could impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.
  • Patients with reproductive potential who do not agree 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" will be based on the Investigator's judgment.
  • Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate or enzalutamide. History of hypersensitivity to docetaxel or polysorbate 80.
  • Known history of mineralocorticoid excess or deficiency (not applicable to patients who have already been treated with abiraterone acetate in first line before inclusion).
  • History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold (not applicable to patients who have already been treated with enzalutamide in first line before inclusion).
  • 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 x 10^9/L.
  • Platelet count <100 x 10^9/L.
  • Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) >1.5 x Upper limit of normal (ULN).
  • Total bilirubin >1.0 x ULN.
  • Potassium <3.5 mmol/L.
  • Serum albumin <3.0 g/dL.
  • Child-Pugh Class B and C.
  • Contraindications to the use of corticosteroid treatment.
  • Symptomatic peripheral neuropathy grade ≥2 NCI CTCAE v4.0.
  • 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 identifier (NCT number): NCT02379390

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United States, Alabama
Investigational Site Number 840030
Muscle Shoals, Alabama, United States, 35661
United States, Alaska
Investigational Site Number 840024
Anchorage, Alaska, United States, 99508
United States, California
Investigational Site Number 840028
Anaheim, California, United States, 92801
Investigational Site Number 840004
Sacramento, California, United States, 95817
United States, Florida
Investigational Site Number 840002
Boca Raton, Florida, United States, 33486
Investigational Site Number 840027
Lakeland, Florida, United States, 33805
Investigational Site Number 840006
Port Saint Lucie, Florida, United States, 34952
United States, Illinois
Investigational Site Number 840015
Ottawa, Illinois, United States, 61350
United States, Louisiana
Investigational Site Number 840001
Covington, Louisiana, United States, 70433
Investigational Site Number 840017
Metairie, Louisiana, United States, 70006
United States, Maryland
Investigational Site Number 840012
Rockville, Maryland, United States, 20850
United States, Nebraska
Investigational Site Number 840026
Omaha, Nebraska, United States, 68198
United States, Ohio
Investigational Site Number 840022
Canton, Ohio, United States, 44718
United States, South Carolina
Investigational Site Number 840016
Myrtle Beach, South Carolina, United States, 29572
Investigational Site Number 124003
Edmonton, Canada, T6G 1Z2
Investigational Site Number 124010
Greenfield Park, Canada, J4V2H1
Investigational Site Number 124005
Hamilton, Canada, L8V 5C2
Investigational Site Number 124004
London, Canada, N6A 4L6
Investigational Site Number 124002
Montreal, Canada, H2L 4M1
Investigational Site Number 124006
Montreal, Canada, H2W1S6
Investigational Site Number 124007
Ottawa, Canada, K1H8L6
Investigational Site Number 124009
Quebec, Canada, G1R 2J6
Investigational Site Number 124008
Saskatoon, Canada, S7N4H4
Investigational Site Number 124001
Vancouver, Canada, N5Z4E6
Sponsors and Collaborators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi Identifier: NCT02379390     History of Changes
Other Study ID Numbers: LPS14022
U1111-1160-6008 ( Other Identifier: UTN )
First Posted: March 4, 2015    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018

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