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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)

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ClinicalTrials.gov Identifier: NCT02379390
Recruitment Status : Terminated (Unsatisfactory patient accrual)
First Posted : March 4, 2015
Results First Posted : June 21, 2019
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate the superiority in term of radiographic Progression-Free Survival (rPFS) of cabazitaxel at at 25 milligram per meter square (mg/m^2) plus prednisone (Arm A) versus either enzalutamide at 160 milligram (mg) once daily or abiraterone acetate at 1000 mg once daily plus prednisone (Arm B) in chemotherapy-naïve participants with metastatic Castration-Resistant Prostate Cancer (mCRPC) who have disease progression while receiving androgen receptor (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 in participants with measurable disease (RECIST 1.1)
  • 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 participant was approximately 2 years. Each participant was treated until radiographic disease progression, unacceptable toxicity, or participants refusal of further study treatment, and each participant was followed after completion of study treatment until death, study cutoff date, or withdrawal of participant 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
Actual 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
Participants received Cabazitaxel 25 mg/m^2, intravenously for 1 hour along with prednisone 10 mg orally on Day 1 of every treatment cycle (each cycle was of 3 weeks) until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
Drug: Cabazitaxel XRP6258
Other Name: Jevtana

Drug: Prednisone
Active Comparator: Abiraterone acetate or Enzalutamide
Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
Drug: Ezalutamide
Other Name: Xtandi

Drug: Abiraterone acetate
Other Name: Zytiga

Drug: Prednisone



Primary Outcome Measures :
  1. Radiographic Progression-Free Survival (rPFS) [ Time Frame: Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days) ]
    rPFS was defined as the time from randomization to the first occurrence of radiological tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or progression of bone lesions using prostate cancer working group 2 (PCWG2) criteria or death due to any cause.


Secondary Outcome Measures :
  1. Number of Participants With Prostate Specific Antigen (PSA) Response [ Time Frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days) ]
    PSA response was defined as decline of serum PSA from baseline by >= 50 percent (%).

  2. Progression-free Survival (PFS) [ Time Frame: Baseline upto progression or death due to any cause (maximum duration: 1059 days) ]
    PFS: time interval between date of randomization to first documentation of tumor progression as per RECIST 1.1.

  3. Overall Survival [ Time Frame: Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days) ]
    Overall Survival was defined as the time interval from the date of randomization to the date of death due to any cause.

  4. Time to PSA Progression [ Time Frame: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days) ]
    Time to PSA progression was defined as the time interval between the date of randomization and the date of first documented PSA progression as per PCWG2 criteria.

  5. Number of Participants Achieving Tumor Response [ Time Frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days) ]
    Tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1.

  6. Duration of Tumor Response [ Time Frame: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days) ]
    Duration of tumor response was defined as the time between the first evaluation at which the tumor response criteria were met and the first documentation of tumor progression.

  7. Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score [ Time Frame: Baseline until the end of study (maximum duration: 1059 days) ]
    Pain response was analyzed using the brief pain inventory-short form (BPI-SF).

  8. Time to Pain Progression [ Time Frame: Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days) ]
    Time to pain progression was defined as the time interval between the date of randomization and the date of the first documented pain progression.

  9. Percentage of Participants With Symptomatic Skeletal Event (SSE) [ Time Frame: Baseline until the end of study (maximum duration: 1059 days) ]
    SSE was the occurrence of a new symptomatic pathological fracture, or the use of external beam radiation to relieve bone pain, or the occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.

  10. Time to Occurrence of Any Symptomatic Skeletal Events (SSE) [ Time Frame: Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days) ]
    Time to SSE was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SSE, whichever is earlier.



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:

  • 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) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart.
  • A PSA value of at least 2 nanogram/milliliter (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.
  • Participants 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 participants 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 participants 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 was 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): NCT02379390


Locations
Show Show 24 study locations
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] February 22, 2016
Statistical Analysis Plan  [PDF] March 29, 2017


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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02379390    
Other Study ID Numbers: LPS14022
U1111-1160-6008 ( Other Identifier: UTN )
First Posted: March 4, 2015    Key Record Dates
Results First Posted: June 21, 2019
Last Update Posted: June 21, 2019
Last Verified: June 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
Prednisone
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
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