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

NCT02379390 | Terminated Phase 2 Results

• 2 other identifiers: LPS14022U1111-1160-6008
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 24

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.

Conditions

Prostate Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-Free Survival (rPFS)

  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.

  Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)

Secondary Outcomes (10)

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

  Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)

• Progression-free Survival (PFS)

  Baseline upto progression or death due to any cause (maximum duration: 1059 days)

• Overall Survival

  Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days)

• Time to PSA Progression

  Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)

• Number of Participants Achieving Tumor Response

  Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)

Study Arms (2)

Cabazitaxel

EXPERIMENTAL

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; Drug: Prednisone

Abiraterone acetate or Enzalutamide

ACTIVE COMPARATOR

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; Drug: Abiraterone acetate; Drug: Prednisone

Interventions

Cabazitaxel XRP6258 DRUG

Also known as: Jevtana

Cabazitaxel

Ezalutamide DRUG

Also known as: Xtandi

Abiraterone acetate or Enzalutamide

Abiraterone acetate DRUG

Also known as: Zytiga

Abiraterone acetate or Enzalutamide

Prednisone DRUG

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:

• 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.

You may not qualify if:

• Less than 28 days elapsed from prior treatment with immunotherapy, radiotherapy, or surgery to 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.
• 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).

Sponsors & Collaborators

• Sanofi: lead

Study Sites (24)

Investigational Site Number 840030

Muscle Shoals, Alabama, 35661, United States

Location

Investigational Site Number 840024

Anchorage, Alaska, 99508, United States

Location

Investigational Site Number 840028

Anaheim, California, 92801, United States

Location

Investigational Site Number 840004

Sacramento, California, 95817, United States

Location

Investigational Site Number 840002

Boca Raton, Florida, 33486, United States

Location

Investigational Site Number 840027

Lakeland, Florida, 33805, United States

Location

Investigational Site Number 840006

Port Saint Lucie, Florida, 34952, United States

Location

Investigational Site Number 840015

Ottawa, Illinois, 61350, United States

Location

Investigational Site Number 840001

Covington, Louisiana, 70433, United States

Location

Investigational Site Number 840017

Metairie, Louisiana, 70006, United States

Location

Investigational Site Number 840012

Rockville, Maryland, 20850, United States

Location

Investigational Site Number 840026

Omaha, Nebraska, 68198, United States

Location

Investigational Site Number 840022

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840016

Myrtle Beach, South Carolina, 29572, United States

Location

Investigational Site Number 124003

Edmonton, T6G 1Z2, Canada

Location

Investigational Site Number 124010

Greenfield Park, J4V2H1, Canada

Location

Investigational Site Number 124005

Hamilton, L8V 5C2, Canada

Location

Investigational Site Number 124004

London, N6A 4L6, Canada

Location

Investigational Site Number 124002

Montreal, H2L 4M1, Canada

Location

Investigational Site Number 124006

Montreal, H2W1S6, Canada

Location

Investigational Site Number 124007

Ottawa, K1H8L6, Canada

Location

Investigational Site Number 124009

Québec, G1R 2J6, Canada

Location

Investigational Site Number 124008

Saskatoon, S7N4H4, Canada

Location

Investigational Site Number 124001

Vancouver, N5Z4E6, Canada

Location

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

Us@sanofipasteur.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: June 17, 2015
• Primary Completion: May 10, 2018
• Study Completion: May 10, 2018
• Last Updated: June 21, 2019
• Results First Posted: June 21, 2019

Record last verified: 2019-06

Locations

CA (10); US (14)