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

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

Sponsors

Lead Sponsor: Sanofi

Source 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.

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.

Overall Status Terminated
Start Date June 17, 2015
Completion Date May 10, 2018
Primary Completion Date May 10, 2018
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Radiographic Progression-Free Survival (rPFS) Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)
Secondary Outcome
Measure Time Frame
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)
Duration of Tumor Response Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score Baseline until the end of study (maximum duration: 1059 days)
Time to Pain Progression Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days)
Percentage of Participants With Symptomatic Skeletal Event (SSE) Baseline until the end of study (maximum duration: 1059 days)
Time to Occurrence of Any Symptomatic Skeletal Events (SSE) Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days)
Enrollment 8
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cabazitaxel XRP6258

Arm Group Label: Cabazitaxel

Other Name: Jevtana

Intervention Type: Drug

Intervention Name: Ezalutamide

Arm Group Label: Abiraterone acetate or Enzalutamide

Other Name: Xtandi

Intervention Type: Drug

Intervention Name: Abiraterone acetate

Arm Group Label: Abiraterone acetate or Enzalutamide

Other Name: Zytiga

Intervention Type: Drug

Intervention Name: Prednisone

Eligibility

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.

Gender: Male

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

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

Canada

United States

Verification Date

June 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Cabazitaxel

Type: Experimental

Description: 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.

Label: Abiraterone acetate or Enzalutamide

Type: Active Comparator

Description: 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.

Acronym PRIMCAB
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov