EFC11784

Sanofi aventis recherche & développement

1 avenue Pierre Brossolette, ChillyMazarin, France, 91380

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Trial Transparency Team, Sanofi aventis recherche & développement, , Contact-US@sanofi.com

No

No

No

Final

27 Jul 2018

No

Yes

29 May 2018

No

To demonstrate the superiority of cabazitaxel plus prednisone at 25 mg/m^2 (Arm A) or 20 mg/m^2 (Arm B) versus docetaxel plus prednisone (Arm C) in terms of overall survival (OS) in subjects with metastatic castration resistant prostate cancer (MCRPC) not previously treated with chemotherapy.

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

17 May 2011

No

Yes

Australia: 103

Belarus: 21

Brazil: 37

Canada: 59

China: 10

Israel: 14

Japan: 18

Mexico: 36

Peru: 10

Russian Federation: 85

Taiwan: 12

Turkey: 5

Ukraine: 67

United States: 85

Poland: 37

Portugal: 34

Romania: 32

Spain: 80

Sweden: 48

Czech Republic: 30

Denmark: 84

Finland: 35

France: 141

Germany: 39

Italy: 46

1168

606

0

0

0

0

0

0

376

784

8

Overall Study (overall period)

Not applicable

Yes

Docetaxel

XRP6976

Solution for infusion

Intravenous use

Docetaxel 75 mg/m^2 in 250 mL dextrose 5% or NaCl 0.9% IV over 1 hour on day 1  of each 21-­day cycle.

Prednisone

Tablet

Oral use

Prednisone 10 mg, once daily in each 21-day cycle.

Cabazitaxel

XRP6258

Jevtana®

Solution for infusion

Intravenous use

Cabazitaxel 20 mg/m^2 in dextrose 5% or NaCl 0.9% IV over 1 hour on Day 1 of each 21-day cycle.

Prednisone

Tablet

Oral use

Prednisone 10 mg, once daily in each 21-day cycle.

Cabazitaxel

XRP6258

Jevtana®

Solution for infusion

Intravenous use

Cabazitaxel 25 mg/m^2 in dextrose 5% or NaCl 0.9% IV over 1 hour on Day 1 of each 21-day cycle.

Prednisone

Tablet

Oral use

Prednisone 10 mg, once daily in each 21-day cycle.

Docetaxel 75 mg/m^2

Cabazitaxel 20 mg/m^2

Cabazitaxel 25 mg/m^2

Docetaxel 75 mg/m^2

Cabazitaxel 20 mg/m^2

Cabazitaxel 25 mg/m^2

OS was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date subject was known to be alive, or at the cut-off date if the subject’s last contact was after the cut-off date. The study cut-off date for the final analysis of OS was the date when the 774th death had been observed. Analysis was performed by Kaplan-Meier method. ITT population that included all the randomized subjects.

Primary

Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months)

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by Eastern Cooperative Oncology Group performance status (ECOG PS) score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 25 mg/m^2 v Docetaxel 75 mg/m^2

779

Pre-specified

0.975

2-sided

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

1.009

2-sided

PFS: time interval between date of randomization to date of first occurrence of any of following events: tumor progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; Prostate Specific Antigen (PSA) progression; pain progression or death due to any cause. Analysis was performed by Kaplan-Meier method. ITT population included all randomized subjects.

Secondary

Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 25 mg/m^2 v Docetaxel 75 mg/m^2

779

Pre-specified

0.989

2-sided

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

1.063

2-sided

Time to tumor progression free survival was defined as the time interval between randomization and the date of first occurrence of tumor progression (assessed using RECIST version 1.1) or death, whichever was earlier. Analysis was performed by Kaplan-Meier method. ITT population included all randomized subjects.

Secondary

Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Docetaxel 75 mg/m^2 v Cabazitaxel 25 mg/m^2

779

Pre-specified

0.958

2-sided

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

0.916

2-sided

Overall objective tumor response was defined as having a partial response (PR) or complete response (CR) according to the RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Analysis was performed on ITT population. Number of subjects analysed=subjects with measurable disease at baseline and at least one valid post-baseline value analysed for specified endpoint.

Secondary

Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Time to PSA-PFS: time interval between date of randomization & first occurrence of PSA progression/ death, whichever was earlier. PSA progression:1) In PSA responders(>=50% decline from baseline PSA of ≥10 ng/mL):increase of ≥25%(at least 2 ng/mL)over nadir value, confirmed by second PSA value at least 3 weeks later;2)In PSA non-responders(not achieved ≥50% decline from baseline PSA ≥10 ng/mL):increase of ≥25% (at least 2 ng/mL) over baseline value, confirmed by second PSA value at least 3 weeks later;3)In subjects not eligible for PSA response(baseline PSA <10 ng/mL):(a)in subjects with baseline PSA>0 ng/mL&<10 ng/mL: increase in PSA by 25% (at least 2 ng/mL) above baseline level, confirmed by second PSA value at least 3weeks apart;(b)in subjects with baseline value=0ng/mL: a post baseline PSA value ≥2ng/mL.Early rise in PSA only indicated progression if it was associated with another sign of DP or if it continued beyond 12 weeks. It was done by Kaplan-Meier method on ITT population.

Secondary

Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 25 mg/m^2 v Docetaxel 75 mg/m^2

779

Pre-specified

0.948

2-sided

Hazard ratio was estimated using a COX Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

1.047

2-sided

PSA response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in subjects with baseline PSA value ≥10 ng/mL. Analysis was performed on ITT population. Number of subjects analysed=subjects with PSA value ≥10 ng/mL at baseline and at least one valid post-baseline value for specified endpoint.

Secondary

Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Time to pain PFS was defined as the time interval between date of randomization and the date of the first occurrence of pain progression or death, whichever was earlier. Pain progression was defined as an increase of ≥1 point in the median present pain intensity (PPI) score from the nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean analgesic score from baseline, due to cancer related pain confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by subject in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the subject in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was done by Kaplan-Meier method on ITT population.

Secondary

Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 25 mg/m^2 v Docetaxel 75 mg/m^2

779

Pre-specified

1.189

2-sided

Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

1.189

2-sided

Pain response was defined as either a ≥2-point decrease from baseline median PPI score without increase in analgesic score, or a ≥50% decrease in analgesic use from baseline mean analgesic score (only in subjects with baseline mean analgesic score≥10) without increase in the pain. Either criterion was maintained for 2 consecutive evaluations at least 3 weeks apart. PPI was rated by subject in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the subject in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was done on ITT population. Number of subjects analysed=subjects with pain score with median PPI ≥2 and/or mean analgesic score≥10 points at baseline and at least one valid post-baseline value for specified endpoint.

Secondary

Baseline until pain progression, death or study cut-off date (maximum duration: 51 months).

SRE free survival was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SRE or death due to any cause, whichever was earlier. SRE were assessed by clinical evaluation. Occurrence of SRE was defined as: pathological fracture(s) and/or spinal cord compression; need for bone irradiation, including radioisotopes or bone surgery; and change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the setting of increased pain) to treat bone pain. Analysis was performed by Kaplan-Meier method on ITT population which included all randomized subjects.

Secondary

Baseline until occurrence of first SRE or death (maximum duration: 51 months)

Hazard ratio was estimated using a COX Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 25 mg/m^2 v Docetaxel 75 mg/m^2

779

Pre-specified

1.121

2-sided

Hazard ratio was estimated using a COX Proportional Hazards regression model. The Cox proportional hazard model was adjusted by ECOG PS score at baseline, measurable disease at baseline, and region with commercial availability of cabazitaxel at the time of randomization.

Cabazitaxel 20 mg/m^2 v Docetaxel 75 mg/m^2

780

Pre-specified

1.014

2-sided

FACT-P was a 39-item subject rated questionnaire that measures the concerns of subjects with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to 156 with higher score indicated better quality of life with fewer symptoms. Analysis was performed on FACT-P population that included all subjects with evaluable individual FACT-P subscale score at baseline and post-baseline on at least 1 of the subscale domains. Here, ‘n’ = subjects with available data for each specified category.

Secondary

Baseline, Day 1 of each cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 (each cycle 21-day); post-treatment follow up 1, 2, 3, 4, 5, 6 (each up to 12 weeks)

FACT-P was a 39-item subject rated questionnaire that measures the concerns of subjects with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). Physical well being, functional well being, and prostate-specific concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms. Analysis was performed on FACT-P population that included all subjects with evaluable individual FACT-P subscale score at baseline and post-baseline on at least 1 of the subscale domains. Here, ‘n’ = subjects with available data for each specified category.

Secondary

Baseline, Day 1 of each cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 (each cycle 21-day); post-treatment follow up 1, 2, 3, 4, 5, 6 (each up to 12 weeks)

All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product.

Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population.

21.0

Docetaxel 75 mg/m^2

Cabazitaxel 20 mg/m^2

Cabazitaxel 25 mg/m^2