Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer (FIRSTANA)

Randomized, Open Label, Multi-Center Study Comparing Cabazitaxel at 25 mg/m^2 and at 20 mg/m^2 in Combination With Prednisone Every 3 Weeks to Docetaxel in Combination With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer Not Pretreated With Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Cabazitaxel (XRP6258); Drug: Prednisone; Drug: Docetaxel (XRP6976)

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.

• Study Type: Interventional
• Enrollment (Actual): 1168
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bankstown, Australia, 2200
    • Investigational Site Number 036016
  • Camperdown, Australia, 2050
    • Investigational Site Number 036008
  • Coffs Harbour, Australia, 2450
    • Investigational Site Number 036015
  • Concord, Australia, 2137
    • Investigational Site Number 036001
  • Fitzroy, Australia, 3065
    • Investigational Site Number 036017
  • Herston, Australia, 4029
    • Investigational Site Number 036003
  • Hornsby, Australia, 2077
    • Investigational Site Number 036010
  • Kurralta Park, Australia, 5037
    • Investigational Site Number 036012
  • Parkville, Australia, 3050
    • Investigational Site Number 036002
  • South Brisbane, Australia, 4101
    • Investigational Site Number 036009
  • Subiaco, Australia, 6008
    • Investigational Site Number 036011
  • Wodonga, Australia, 3690
    • Investigational Site Number 036013
• Belarus
  • Minsk, Belarus, 220013
    • Investigational Site Number 112001
  • Minsk, Belarus, 223040
    • Investigational Site Number 112002
  • Vitebsk, Belarus, 210603
    • Investigational Site Number 112004
• Brazil
  • Passo Fundo, Brazil, 99010-260
    • Investigational Site Number 076006
  • Porto Alegre, Brazil, 90035-001
    • Investigational Site Number 076001
  • Porto Alegre, Brazil, 90610-000
    • Investigational Site Number 076002
  • Rio De Janeiro, Brazil, 20230-130
    • Investigational Site Number 076004
  • Sao Jose Do Rio Preto, Brazil, 15090-000
    • Investigational Site Number 076009
  • Sao Paulo, Brazil, 01246-000
    • Investigational Site Number 076005
  • Uberlandia, Brazil, 38408 150
    • Investigational Site Number 076003
• Canada
  • London, Canada, N6A 4L6
    • Investigational Site Number 124002
  • Mississauga, Canada, L5M 2N1
    • Investigational Site Number 124007
  • Moncton, Canada, E1C 6Z8
    • Investigational Site Number 124005
  • Montreal, Canada, H2L 4M1
    • Investigational Site Number 124003
  • Quebec, Canada, G1R 2J6
    • Investigational Site Number 124004
  • Toronto, Canada, M4N 3M5
    • Investigational Site Number 124006
• China
  • Beijing, China, 100034
    • Investigational Site Number 156005
  • Shanghai, China, 200032
    • Investigational Site Number 156002
  • Shanghai, China, 200040
    • Investigational Site Number 156003
  • Shanghai, China, 200040
    • Investigational Site Number 156004
• Czechia
  • Brno, Czechia, 65653
    • Investigational Site Number 203002
  • Novy Jicin, Czechia, 74101
    • Investigational Site Number 203003
  • Olomouc, Czechia, 77520
    • Investigational Site Number 203001
  • Praha 2, Czechia, 12808
    • Investigational Site Number 203004
• Denmark
  • Herlev, Denmark, 2730
    • Investigational Site Number 208002
  • København Ø, Denmark, 2100
    • Investigational Site Number 208001
  • Odense C, Denmark, 5000
    • Investigational Site Number 208003
  • Ålborg, Denmark, 9100
    • Investigational Site Number 208004
• Finland
  • Helsinki, Finland, 00290
    • Investigational Site Number 246002
  • Kuopio, Finland, 70210
    • Investigational Site Number 246001
  • Turku, Finland, FIN-20520
    • Investigational Site Number 246003
• France
  • Besancon Cedex, France, 25030
    • Investigational Site Number 250010
  • Bordeaux Cedex, France, 33076
    • Investigational Site Number 250002
  • Caen Cedex 05, France, 14076
    • Investigational Site Number 250006
  • Lyon, France, 69373
    • Investigational Site Number 250005
  • Paris Cedex 05, France, 75231
    • Investigational Site Number 250003
  • Paris Cedex 10, France, 75475
    • Investigational Site Number 250004
  • Paris Cedex 15, France, 75908
    • Investigational Site Number 250001
  • Poitiers Cedex, France, 86021
    • Investigational Site Number 250007
  • Suresnes, France, 92151
    • Investigational Site Number 250008
  • Villejuif, France, 94805
    • Investigational Site Number 250009
• Germany
  • Aachen, Germany, 52074
    • Investigational Site Number 276003
  • Berlin, Germany, 14197
    • Investigational Site Number 276005
  • Düsseldorf, Germany, 40225
    • Investigational Site Number 276001
  • Erlangen, Germany, 91054
    • Investigational Site Number 276004
  • Homburg, Germany, 66421
    • Investigational Site Number 276002
  • München, Germany, 81675
    • Investigational Site Number 276006
• Israel
  • Kfar Saba, Israel, 44281
    • Investigational Site Number 376004
  • Petah-Tikva, Israel, 49100
    • Investigational Site Number 376003
  • Tel Aviv, Israel, 64239
    • Investigational Site Number 376002
• Italy
  • Arezzo, Italy, 06156
    • Investigational Site Number 380001
  • Bari, Italy, 70124
    • Investigational Site Number 380004
  • Orbassano, Italy, 10043
    • Investigational Site Number 380003
  • Roma, Italy, 00144
    • Investigational Site Number 380005
  • Trento, Italy, 38100
    • Investigational Site Number 380002
• Japan
  • Bunkyo-Ku, Japan
    • Investigational Site Number 392001
  • Chiba-Shi, Japan
    • Investigational Site Number 392003
  • Kashiwa-Shi, Japan
    • Investigational Site Number 392006
  • Koto-Ku, Japan
    • Investigational Site Number 392005
  • Osaka Sayama-Shi, Japan
    • Investigational Site Number 392002
  • Osaka-Shi, Japan
    • Investigational Site Number 392004
• Mexico
  • Acapulco, Mexico, 39670
    • Investigational Site Number 484007
  • Aguascalientes, Mexico, 20230
    • Investigational Site Number 484008
  • D.f., Mexico, 14080
    • Investigational Site Number 484003
  • Guadalajara, Mexico, 44280
    • Investigational Site Number 484004
  • Merida, Mexico, 97134
    • Investigational Site Number 484009
  • Queretaro, Mexico, 76000
    • Investigational Site Number 484005
  • San Luis Potosi, Mexico
    • Investigational Site Number 484002
  • Zapopan, Mexico, 45040
    • Investigational Site Number 484006
• Peru
  • Lima, Peru, LIMA 34
    • Investigational Site Number 604002
  • Lima, Peru, 027
    • Investigational Site Number 604006
  • Lima, Peru, 041
    • Investigational Site Number 604001
  • Lima, Peru, LIMA 01
    • Investigational Site Number 604005
• Poland
  • Bydgoszcz, Poland, 85-796
    • Investigational Site Number 616002
  • Gdansk, Poland, 80-952
    • Investigational Site Number 616001
  • Koscierzyna, Poland, 83-400
    • Investigational Site Number 616003
  • Lodz, Poland, 93-509
    • Investigational Site Number 616005
  • Poznan, Poland, 61-485
    • Investigational Site Number 616004
• Portugal
  • Coimbra, Portugal, 3049
    • Investigational Site Number 620003
  • Lisboa, Portugal, 1649-035
    • Investigational Site Number 620004
  • Lisboa, Portugal, 1099-023
    • Investigational Site Number 620005
  • Porto, Portugal, 4200
    • Investigational Site Number 620001
  • Porto, Portugal, 4200
    • Investigational Site Number 620002
• Romania
  • Baia Mare, Romania, 430031
    • Investigational Site Number 642004
  • Bucharest, Romania, 022328
    • Investigational Site Number 642008
  • Bucuresti, Romania, 022328
    • Investigational Site Number 642005
  • Cluj Napoca, Romania, 400015
    • Investigational Site Number 642003
  • Cluj Napoca, Romania, 400015
    • Investigational Site Number 642002
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642007
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Investigational Site Number 643004
  • Moscow, Russian Federation, 129128
    • Investigational Site Number 643008
  • Omsk, Russian Federation, 644013
    • Investigational Site Number 643003
  • Pyatigorsk, Russian Federation, 357502
    • Investigational Site Number 643002
  • Ryazan, Russian Federation, 390011
    • Investigational Site Number 643007
  • St-Petersburg, Russian Federation, 197758
    • Investigational Site Number 643005
  • Tomsk, Russian Federation, 634028
    • Investigational Site Number 643001
  • Yaroslavl, Russian Federation, 150054
    • Investigational Site Number 643006
• Spain
  • Barcelona, Spain, 08036
    • Investigational Site Number 724002
  • Barcelona, Spain, 08003
    • Investigational Site Number 724001
  • Barcelona, Spain, 08025
    • Investigational Site Number 724007
  • Hospitalet De Llobregat, Spain, 08907
    • Investigational Site Number 724003
  • Madrid, Spain, 28041
    • Investigational Site Number 724004
  • Madrid, Spain, 28007
    • Investigational Site Number 724005
  • Santiago De Compostela, Spain, 15706
    • Investigational Site Number 724006
• Sweden
  • Malmö, Sweden, 205 02
    • Investigational Site Number 752003
  • Stockholm, Sweden, 171 76
    • Investigational Site Number 752002
  • Uppsala, Sweden, 751 85
    • Investigational Site Number 752001
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Investigational Site Number 158004
  • Taichung, Taiwan, 407
    • Investigational Site Number 158002
  • Taipei, Taiwan
    • Investigational Site Number 158001
  • Tao-Yuan, Taiwan, 333
    • Investigational Site Number 158003
• Turkey
  • Ankara, Turkey, 06100
    • Investigational Site Number 792002
  • Istanbul, Turkey, 34303
    • Investigational Site Number 792001
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Investigational Site Number 804009
  • Dnipropetrovsk, Ukraine, 49102
    • Investigational Site Number 804004
  • Donetsk, Ukraine, 83092
    • Investigational Site Number 804010
  • Ivano-Frankivsk, Ukraine, 76018
    • Investigational Site Number 804006
  • Kharkov, Ukraine, 61037
    • Investigational Site Number 804003
  • Kyiv, Ukraine, 01133
    • Investigational Site Number 804002
  • Kyiv, Ukraine, 1601
    • Investigational Site Number 804001
  • Lutsk, Ukraine, 43018
    • Investigational Site Number 804007
  • Uzhgorod, Ukraine, 88000
    • Investigational Site Number 804005
  • Zaporizhzhya, Ukraine, 69040
    • Investigational Site Number 804008
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35661
      • Investigational Site Number 840004
  • California
    • Anaheim, California, United States, 92801
      • Investigational Site Number 840009
    • Bakersfield, California, United States, 93309
      • Investigational Site Number 840014
    • Sacramento, California, United States, 95816
      • Investigational Site Number 840030
    • San Bernardino, California, United States, 92404
      • Investigational Site Number 840003
    • San Francisco, California, United States, 94143
      • Investigational Site Number 840012
  • Colorado
    • Denver, Colorado, United States, 80262
      • Investigational Site Number 840019
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Investigational Site Number 840013
    • Jacksonville, Florida, United States, 32256
      • Investigational Site Number 840035
    • Port Saint Lucie, Florida, United States, 34952
      • Investigational Site Number 840001
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Investigational Site Number 840015
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Investigational Site Number 840018
  • Kentucky
    • Paducah, Kentucky, United States, 42002
      • Investigational Site Number 840010
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Investigational Site Number 840008
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Investigational Site Number 840006
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Investigational Site Number 840238
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 840138
    • Brookline, Massachusetts, United States, 02115
      • Investigational Site Number 840038
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Investigational Site Number 840005
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Investigational Site Number 840021
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Investigational Site Number 840016
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Investigational Site Number 840020
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Investigational Site Number 840017
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Investigational Site Number 840033
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Investigational Site Number 840036
    • Washington, North Carolina, United States, 27889
      • Investigational Site Number 840011
  • Ohio
    • Akron, Ohio, United States, 44302
      • Investigational Site Number 840026
    • Cleveland, Ohio, United States, 44106
      • Investigational Site Number 840023
  • Pennsylvania
    • Dunmore, Pennsylvania, United States, 18512
      • Investigational Site Number 840032
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Investigational Site Number 840007
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Investigational Site Number 840037
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Investigational Site Number 840028

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria :

• I 01. Histologically- or cytologically-confirmed prostate adenocarcinoma.
• I 02. Metastatic disease.
• I 03. Progressive disease while receiving hormonal therapy or after surgical castration.
• I 04. Effective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone (LHRH) agonists or antagonist with or without anti-androgens.

Exclusion criteria:

• E 01. Prior chemotherapy for prostate cancer,
• E 02. Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of randomization. Participants on biphosphonates prior to study entry.
• E 03. Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
• E 04. 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 [NCI CTCAE] v4.03) at the time of randomization.
• E 05. Less than 18 years (or country's legal age of majority if the legal age is >18 years).
• E 06. Eastern Cooperative Oncology Group (ECOG) performance status >2.
• E 07. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• E 08. Prior malignancy.
• E 09. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
• E 10. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
• E 11. Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
• E 12. Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
• E 13. Any severe acute or chronic medical condition which could impair the ability of the participant to participate to the study or interfere with interpretation of study results, or participants unable to comply with the study procedures.
• E 14. Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent form prior to enrollment into the study.
• E 15. Participants with reproductive potential who did not agree to use accepted and effective method of contraception during the study treatment period.
• E 16. History of hypersensitivity to docetaxel, or polysorbate 80.
• E 17. Inadequate organ and bone marrow function
• E 18. Contraindications to the use of corticosteroid treatment.
• E 19. Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.4.03).

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cabazitaxel 25 mg/m^2; 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.	Drug: Cabazitaxel (XRP6258); Pharmaceutical form: Solution for injection; Route of administration: Intravenous; Drug: Prednisone; Pharmaceutical form: Tablet; Route of administration: Oral
EXPERIMENTAL: Cabazitaxel 20 mg/m^2; 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.	Drug: Cabazitaxel (XRP6258); Pharmaceutical form: Solution for injection; Route of administration: Intravenous; Drug: Prednisone; Pharmaceutical form: Tablet; Route of administration: Oral
ACTIVE_COMPARATOR: Docetaxel 75 mg/m^2; 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.	Drug: Prednisone; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Docetaxel (XRP6976); Pharmaceutical form: Solution for injection'; Route of administration: Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	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.	Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)
Time to Tumor Progression Free Survival	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.	Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Percentage of Participants With Overall Objective Tumor Response	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.	Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS)	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.	Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Percentage of Participants With PSA Response	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.	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 Progression Free Survival (Pain PFS)	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.	Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)
Percentage of Participants With Pain Response	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.	Baseline until pain progression, death or study cut-off date (maximum duration: 51 months)
Skeletal Related Events (SRE) Free Survival	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.	Baseline until occurrence of first SRE or death (maximum duration: 51 months)
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL)	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.	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)
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL	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.	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)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.
• Thiery-Vuillemin A, Fizazi K, Sartor O, Oudard S, Bury D, Thangavelu K, Ozatilgan A, Poole EM, Eisenberger M, de Bono J. An analysis of health-related quality of life in the phase III PROSELICA and FIRSTANA studies assessing cabazitaxel in patients with metastatic castration-resistant prostate cancer. ESMO Open. 2021 Apr;6(2):100089. doi: 10.1016/j.esmoop.2021.100089. Epub 2021 Mar 16.
• Mehra N, Dolling D, Sumanasuriya S, Christova R, Pope L, Carreira S, Seed G, Yuan W, Goodall J, Hall E, Flohr P, Boysen G, Bianchini D, Sartor O, Eisenberger MA, Fizazi K, Oudard S, Chadjaa M, Mace S, de Bono JS. Plasma Cell-free DNA Concentration and Outcomes from Taxane Therapy in Metastatic Castration-resistant Prostate Cancer from Two Phase III Trials (FIRSTANA and PROSELICA). Eur Urol. 2018 Sep;74(3):283-291. doi: 10.1016/j.eururo.2018.02.013. Epub 2018 Feb 28.
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Study record dates

Study Major Dates

• Study Start (ACTUAL): May 5, 2011
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): May 1, 2018

Study Registration Dates

• First Submitted: March 3, 2011
• First Submitted That Met QC Criteria: March 3, 2011
• First Posted (ESTIMATE): March 4, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2019
• Last Update Submitted That Met QC Criteria: May 21, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: EFC11784; 2010-022064-12 (EUDRACT_NUMBER); U1111-1117-8356 (OTHER: UTN)