Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT01308567
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
* 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 term of overall survival (OS) in participants with metastatic castration resistant prostate cancer (mCRPC) and not previously treated with chemotherapy.
Secondary Objectives:
* To evaluate safety in the 3 treatment arms.
* To compare efficacy of cabazitaxel at 20 mg/m\^2 and 25 mg/m\^2 to docetaxel for:
* Progression Free Survival (PFS) (RECIST 1.1)
* Tumor progression free survival (RECIST 1.1)
* Tumor response in participants with measurable disease (RECIST 1.1),
* PSA response
* PSA-Progression free survival (PSA-PFS).
* Pain response in participants with stable pain at baseline
* Pain progression free survival
* Time to occurrence of any skeletal related events (SRE)
* To compare Health-Related Quality of Life (HRQL).
* To assess the pharmacokinetics and pharmacogenomics of cabazitaxel.
- Detailed Description
Participants were treated until progressive disease, unacceptable toxicity, or participant's refusal of further study treatment. All participants were followed when on study treatment and after completion of study treatment during follow up period until death or the study cutoff date, whichever comes first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1168
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cabazitaxel 25 mg/m^2 Cabazitaxel (XRP6258) Cabazitaxel 25 mg/m\^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until disease progression (DP), unacceptable toxicity or participant's refusal. Cabazitaxel 20 mg/m^2 Cabazitaxel (XRP6258) Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal. Docetaxel 75 mg/m^2 Docetaxel (XRP6976) Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal. Cabazitaxel 25 mg/m^2 Prednisone Cabazitaxel 25 mg/m\^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until disease progression (DP), unacceptable toxicity or participant's refusal. Cabazitaxel 20 mg/m^2 Prednisone Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal. Docetaxel 75 mg/m^2 Prednisone Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months ) 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 participant was known to be alive, or at the cut-off date if the participant'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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months) 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.
Time to Tumor Progression Free Survival Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months) 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.
Percentage of Participants With Overall Objective Tumor Response Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months) 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.
Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS) 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 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 participants not eligible for PSA response(baseline PSA \<10 ng/mL):(a)in participants 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 participants 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. Analysis performed by Kaplan-Meier method.
Skeletal Related Events (SRE) Free Survival Baseline until occurrence of first SRE or death (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.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) 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 participant rated questionnaire that measures the concerns of participants 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 to156 with higher score indicated better quality of life with fewer symptoms.
Percentage of Participants With PSA Response Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months) 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 participants with baseline PSA value ≥10 ng/mL.
Time to Pain Progression Free Survival (Pain PFS) Baseline until disease progression, death or study cut-off date (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 participant 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 participant 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 performed by Kaplan-Meier method.
Percentage of Participants With Pain Response Baseline until pain progression, death or study cut-off date (maximum duration: 51 months) 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 participants 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 participant 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 participant 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.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL 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 participant rated questionnaire that measures the concerns of participants 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.
Trial Locations
- Locations (167)
Investigational Site Number 250010
🇫🇷Besancon Cedex, France
Investigational Site Number 840035
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 112001
🇧🇾Minsk, Belarus
Investigational Site Number 203004
🇨🇿Praha 2, Czechia
Investigational Site Number 036017
🇦🇺Fitzroy, Australia
Investigational Site Number 076009
🇧🇷Sao Jose Do Rio Preto, Brazil
Investigational Site Number 036003
🇦🇺Herston, Australia
Investigational Site Number 036011
🇦🇺Subiaco, Australia
Investigational Site Number 076006
🇧🇷Passo Fundo, Brazil
Investigational Site Number 840026
🇺🇸Akron, Ohio, United States
Investigational Site Number 036016
🇦🇺Bankstown, Australia
Investigational Site Number 036015
🇦🇺Coffs Harbour, Australia
Investigational Site Number 076005
🇧🇷Sao Paulo, Brazil
Investigational Site Number 036002
🇦🇺Parkville, Australia
Investigational Site Number 124007
🇨🇦Mississauga, Canada
Investigational Site Number 124005
🇨🇦Moncton, Canada
Investigational Site Number 208001
🇩🇰København Ø, Denmark
Investigational Site Number 112004
🇧🇾Vitebsk, Belarus
Investigational Site Number 203003
🇨🇿Novy Jicin, Czechia
Investigational Site Number 076003
🇧🇷Uberlandia, Brazil
Investigational Site Number 124004
🇨🇦Quebec, Canada
Investigational Site Number 036009
🇦🇺South Brisbane, Australia
Investigational Site Number 124002
🇨🇦London, Canada
Investigational Site Number 250002
🇫🇷Bordeaux Cedex, France
Investigational Site Number 840004
🇺🇸Muscle Shoals, Alabama, United States
Investigational Site Number 840036
🇺🇸Raleigh, North Carolina, United States
Investigational Site Number 156002
🇨🇳Shanghai, China
Investigational Site Number 208004
🇩🇰Ålborg, Denmark
Investigational Site Number 840017
🇺🇸East Orange, New Jersey, United States
Investigational Site Number 840032
🇺🇸Dunmore, Pennsylvania, United States
Investigational Site Number 156005
🇨🇳Beijing, China
Investigational Site Number 840037
🇺🇸Myrtle Beach, South Carolina, United States
Investigational Site Number 156004
🇨🇳Shanghai, China
Investigational Site Number 036008
🇦🇺Camperdown, Australia
Investigational Site Number 124003
🇨🇦Montreal, Canada
Investigational Site Number 036010
🇦🇺Hornsby, Australia
Investigational Site Number 036013
🇦🇺Wodonga, Australia
Investigational Site Number 250005
🇫🇷Lyon, France
Investigational Site Number 246003
🇫🇮Turku, Finland
Investigational Site Number 392004
🇯🇵Osaka-Shi, Japan
Investigational Site Number 643007
🇷🇺Ryazan, Russian Federation
Investigational Site Number 376003
🇮🇱Petah-Tikva, Israel
Investigational Site Number 250004
🇫🇷Paris Cedex 10, France
Investigational Site Number 276006
🇩🇪München, Germany
Investigational Site Number 250007
🇫🇷Poitiers Cedex, France
Investigational Site Number 250008
🇫🇷Suresnes, France
Investigational Site Number 246002
🇫🇮Helsinki, Finland
Investigational Site Number 380004
🇮🇹Bari, Italy
Investigational Site Number 643005
🇷🇺St-Petersburg, Russian Federation
Investigational Site Number 246001
🇫🇮Kuopio, Finland
Investigational Site Number 276004
🇩🇪Erlangen, Germany
Investigational Site Number 484003
🇲🇽D.f., Mexico
Investigational Site Number 484005
🇲🇽Queretaro, Mexico
Investigational Site Number 380003
🇮🇹Orbassano, Italy
Investigational Site Number 392003
🇯🇵Chiba-Shi, Japan
Investigational Site Number 276002
🇩🇪Homburg, Germany
Investigational Site Number 376002
🇮🇱Tel Aviv, Israel
Investigational Site Number 250001
🇫🇷Paris Cedex 15, France
Investigational Site Number 484002
🇲🇽San Luis Potosi, Mexico
Investigational Site Number 616002
🇵🇱Bydgoszcz, Poland
Investigational Site Number 392001
🇯🇵Bunkyo-Ku, Japan
Investigational Site Number 276001
🇩🇪Düsseldorf, Germany
Investigational Site Number 376004
🇮🇱Kfar Saba, Israel
Investigational Site Number 643003
🇷🇺Omsk, Russian Federation
Investigational Site Number 620001
🇵🇹Porto, Portugal
Investigational Site Number 804003
🇺🇦Kharkov, Ukraine
Investigational Site Number 642005
🇷🇴Bucuresti, Romania
Investigational Site Number 158002
🇨🇳Taichung, Taiwan
Investigational Site Number 724002
🇪🇸Barcelona, Spain
Investigational Site Number 840023
🇺🇸Cleveland, Ohio, United States
Investigational Site Number 484004
🇲🇽Guadalajara, Mexico
Investigational Site Number 484009
🇲🇽Merida, Mexico
Investigational Site Number 484006
🇲🇽Zapopan, Mexico
Investigational Site Number 620003
🇵🇹Coimbra, Portugal
Investigational Site Number 620004
🇵🇹Lisboa, Portugal
Investigational Site Number 620002
🇵🇹Porto, Portugal
Investigational Site Number 804002
🇺🇦Kyiv, Ukraine
Investigational Site Number 840012
🇺🇸San Francisco, California, United States
Investigational Site Number 156003
🇨🇳Shanghai, China
Investigational Site Number 840005
🇺🇸Detroit, Michigan, United States
Investigational Site Number 208002
🇩🇰Herlev, Denmark
Investigational Site Number 208003
🇩🇰Odense C, Denmark
Investigational Site Number 250009
🇫🇷Villejuif, France
Investigational Site Number 392005
🇯🇵Koto-Ku, Japan
Investigational Site Number 840009
🇺🇸Anaheim, California, United States
Investigational Site Number 840014
🇺🇸Bakersfield, California, United States
Investigational Site Number 840013
🇺🇸Boca Raton, Florida, United States
Investigational Site Number 840001
🇺🇸Port Saint Lucie, Florida, United States
Investigational Site Number 840018
🇺🇸Wichita, Kansas, United States
Investigational Site Number 840015
🇺🇸Decatur, Illinois, United States
Investigational Site Number 840238
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 840006
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840010
🇺🇸Paducah, Kentucky, United States
Investigational Site Number 840138
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 840020
🇺🇸Lincoln, Nebraska, United States
Investigational Site Number 840033
🇺🇸Albuquerque, New Mexico, United States
Investigational Site Number 840021
🇺🇸Saint Louis Park, Minnesota, United States
Investigational Site Number 840016
🇺🇸Kansas City, Missouri, United States
Investigational Site Number 840011
🇺🇸Washington, North Carolina, United States
Investigational Site Number 036012
🇦🇺Kurralta Park, Australia
Investigational Site Number 203001
🇨🇿Olomouc, Czechia
Investigational Site Number 250006
🇫🇷Caen Cedex 05, France
Investigational Site Number 380001
🇮🇹Arezzo, Italy
Investigational Site Number 392006
🇯🇵Kashiwa-Shi, Japan
Investigational Site Number 380002
🇮🇹Trento, Italy
Investigational Site Number 380005
🇮🇹Roma, Italy
Investigational Site Number 392002
🇯🇵Osaka Sayama-Shi, Japan
Investigational Site Number 643004
🇷🇺Ekaterinburg, Russian Federation
Investigational Site Number 643002
🇷🇺Pyatigorsk, Russian Federation
Investigational Site Number 643001
🇷🇺Tomsk, Russian Federation
Investigational Site Number 642007
🇷🇴Hunedoara, Romania
Investigational Site Number 643008
🇷🇺Moscow, Russian Federation
Investigational Site Number 643006
🇷🇺Yaroslavl, Russian Federation
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724005
🇪🇸Madrid, Spain
Investigational Site Number 724003
🇪🇸Hospitalet De Llobregat, Spain
Investigational Site Number 724007
🇪🇸Barcelona, Spain
Investigational Site Number 752003
🇸🇪Malmö, Sweden
Investigational Site Number 724004
🇪🇸Madrid, Spain
Investigational Site Number 724006
🇪🇸Santiago De Compostela, Spain
Investigational Site Number 752002
🇸🇪Stockholm, Sweden
Investigational Site Number 158004
🇨🇳Kaohsiung, Taiwan
Investigational Site Number 804006
🇺🇦Ivano-Frankivsk, Ukraine
Investigational Site Number 752001
🇸🇪Uppsala, Sweden
Investigational Site Number 158001
🇨🇳Taipei, Taiwan
Investigational Site Number 792002
🇹🇷Ankara, Turkey
Investigational Site Number 158003
🇨🇳Tao-Yuan, Taiwan
Investigational Site Number 792001
🇹🇷Istanbul, Turkey
Investigational Site Number 804009
🇺🇦Cherkasy, Ukraine
Investigational Site Number 804004
🇺🇦Dnipropetrovsk, Ukraine
Investigational Site Number 804010
🇺🇦Donetsk, Ukraine
Investigational Site Number 804005
🇺🇦Uzhgorod, Ukraine
Investigational Site Number 804001
🇺🇦Kyiv, Ukraine
Investigational Site Number 804007
🇺🇦Lutsk, Ukraine
Investigational Site Number 804008
🇺🇦Zaporizhzhya, Ukraine
Investigational Site Number 840028
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 036001
🇦🇺Concord, Australia
Investigational Site Number 076001
🇧🇷Porto Alegre, Brazil
Investigational Site Number 840003
🇺🇸San Bernardino, California, United States
Investigational Site Number 840038
🇺🇸Brookline, Massachusetts, United States
Investigational Site Number 840008
🇺🇸New Orleans, Louisiana, United States
Investigational Site Number 276003
🇩🇪Aachen, Germany
Investigational Site Number 276005
🇩🇪Berlin, Germany
Investigational Site Number 076002
🇧🇷Porto Alegre, Brazil
Investigational Site Number 076004
🇧🇷Rio De Janeiro, Brazil
Investigational Site Number 124006
🇨🇦Toronto, Canada
Investigational Site Number 203002
🇨🇿Brno, Czechia
Investigational Site Number 250003
🇫🇷Paris Cedex 05, France
Investigational Site Number 840030
🇺🇸Sacramento, California, United States
Investigational Site Number 840019
🇺🇸Denver, Colorado, United States
Investigational Site Number 616005
🇵🇱Lodz, Poland
Investigational Site Number 484008
🇲🇽Aguascalientes, Mexico
Investigational Site Number 604006
🇵🇪Lima, Peru
Investigational Site Number 604005
🇵🇪Lima, Peru
Investigational Site Number 616001
🇵🇱Gdansk, Poland
Investigational Site Number 112002
🇧🇾Minsk, Belarus
Investigational Site Number 604001
🇵🇪Lima, Peru
Investigational Site Number 604002
🇵🇪Lima, Peru
Investigational Site Number 616004
🇵🇱Poznan, Poland
Investigational Site Number 642004
🇷🇴Baia Mare, Romania
Investigational Site Number 642002
🇷🇴Cluj Napoca, Romania
Investigational Site Number 484007
🇲🇽Acapulco, Mexico
Investigational Site Number 616003
🇵🇱Koscierzyna, Poland
Investigational Site Number 620005
🇵🇹Lisboa, Portugal
Investigational Site Number 642008
🇷🇴Bucharest, Romania
Investigational Site Number 642003
🇷🇴Cluj Napoca, Romania
Investigational Site Number 840007
🇺🇸Pawtucket, Rhode Island, United States