Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer (PROSELICA)

Randomized, Open Label Multi-Center Study Comparing Cabazitaxel at 20 mg/m² and at 25 mg/m² Every 3 Weeks in Combination With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen

Primary Objective:

- To demonstrate the non inferiority in term of overall survival (OS) of Cabazitaxel 20 mg/m² (Arm A) versus Cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in participants with metastatic castration resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen.

Secondary Objectives:

• To evaluate safety in the 2 treatment arms and to assess if Cabazitaxel 20 mg/m² was better tolerated than Cabazitaxel 25 mg/m².

• To compare efficacy of Cabazitaxel at 20 mg/m² and 25 mg/m² for:

  • Progression Free Survival (PFS) defined as the first occurrence of any of the following events: tumor progression per Response Evaluation Criteria In Solid Tumors (RECIST), prostate-specific antigen (PSA) progression, pain progression or death due to any cause;
  • PSA Progression;
  • Pain progression;
  • Tumor response in participants with measurable disease (RECIST 1.1);
  • PSA response;
  • Pain response in participants with stable pain at baseline.
• To compare Health-related Quality of Life (HRQoL).
• To assess the pharmacokinetics and pharmacogenomics of Cabazitaxel.

Study Overview

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

Detailed Description

Participants were treated until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles. 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 came first.

• Study Type: Interventional
• Enrollment (Actual): 1200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1120AAT
    • Investigational Site Number 032002
  • Rosario, Argentina, 2000
    • Investigational Site Number 032001
  • Salta, Argentina, A4406CLA
    • Investigational Site Number 032003
  • Santa Fe, Argentina, 3000
    • Investigational Site Number 032004
• Australia
  • Adelaide, Australia, 5000
    • Investigational Site Number 036014
  • Bankstown, Australia, 2200
    • Investigational Site Number 036013
  • Box Hill, Australia, 3128
    • Investigational Site Number 036010
  • Camperdown, Australia, 2050
    • Investigational Site Number 036012
  • Coffs Harbour, Australia, 2450
    • Investigational Site Number 036008
  • Concord, Australia, 2137
    • Investigational Site Number 036001
  • Elizabeth Vale, Australia, 5112
    • Investigational Site Number 036015
  • Fitzroy, Australia, 3065
    • Investigational Site Number 036009
  • Garran, Australia, 2605
    • Investigational Site Number 036007
  • Heidelberg West, Australia, 3081
    • Investigational Site Number 036005
  • Malvern, Australia, 3144
    • Investigational Site Number 036002
  • South Brisbane, Australia, 4101
    • Investigational Site Number 036006
  • Subiaco, Australia, 6008
    • Investigational Site Number 036016
  • Wahroonga, Australia, 2076
    • Investigational Site Number 036003
  • Wodonga, Australia, 3690
    • Investigational Site Number 036004
• Belgium
  • Antwerpen, Belgium, B-2020
    • Investigational Site Number 056007
  • Brussel, Belgium, 1090
    • Investigational Site Number 056008
  • Bruxelles, Belgium, 1000
    • Investigational Site Number 056001
  • Bruxelles, Belgium, 1200
    • Investigational Site Number 056002
  • Charleroi, Belgium, B-6000
    • Investigational Site Number 056009
  • Gent, Belgium, 9000
    • Investigational Site Number 056003
  • Godinne, Belgium, B-5530
    • Investigational Site Number 056012
  • Haine-Saint-Paul, Belgium, 7100
    • Investigational Site Number 056016
  • Hasselt, Belgium, B-3500
    • Investigational Site Number 056005
  • Libramont, Belgium, 6800
    • Investigational Site Number 056010
  • Liège, Belgium, 4000
    • Investigational Site Number 056013
  • Ottignies, Belgium, 1340
    • Investigational Site Number 056011
  • Roeselare, Belgium, 8800
    • Investigational Site Number 056004
  • Turnhout, Belgium, B-2300
    • Investigational Site Number 056006
• Brazil
  • Fortaleza, Brazil
    • Investigational Site Number 076016
  • Ijui, Brazil, 98700 000
    • Investigational Site Number 076012
  • Mogi Das Cruzes, Brazil, 08730-500
    • Investigational Site Number 076015
  • Porto Alegre, Brazil, 90110-270
    • Investigational Site Number 076014
  • Rio De Janeiro, Brazil, 22793-080
    • Investigational Site Number 076010
  • Salvador, Brazil, 41256-900
    • Investigational Site Number 076007
  • Sao Jose Do Rio Preto, Brazil, 15090-000
    • Investigational Site Number 076003
  • Sao Paulo, Brazil, 01221-020
    • Investigational Site Number 076009
  • Sao Paulo, Brazil, 01308050
    • Investigational Site Number 076001
  • Sao Paulo, Brazil, 01321-001
    • Investigational Site Number 076013
  • Sao Paulo, Brazil, 01509-900
    • Investigational Site Number 076008
  • Sao Paulo, Brazil, 03102-002
    • Investigational Site Number 076002
• Canada
  • Greenfield Park, Canada, J4V 2H1
    • Investigational Site Number 124002
  • Oshawa, Canada, L1G 2B9
    • Investigational Site Number 124001
  • Ottawa, Canada, K1H 8L6
    • Investigational Site Number 124003
  • Owen Sound, Canada, N4K 2J1
    • Investigational Site Number 124005
• Chile
  • Santiago, Chile, 8380456
    • Investigational Site Number 152002
  • Santiago, Chile, 751-0009
    • Investigational Site Number 152005
  • Santiago, Chile, 7510032
    • Investigational Site Number 152004
  • Viña Del Mar, Chile, 2540364
    • Investigational Site Number 152001
• France
  • Avignon Cedex 9, France, 84918
    • Investigational Site Number 250005
  • Hyeres, France, 83400
    • Investigational Site Number 250008
  • La Roche Sur Yon, France, 85925
    • Investigational Site Number 250001
  • Nantes Cedex 2, France, 44202
    • Investigational Site Number 250002
  • Nimes, France, 30029
    • Investigational Site Number 250004
  • Paris, France, 75014
    • Investigational Site Number 250010
  • Reims, France, 51100
    • Investigational Site Number 250007
  • Reims Cedex, France, 51056
    • Investigational Site Number 250009
  • Saint Brieuc Cedex, France, 22015
    • Investigational Site Number 250006
  • Toulouse Cedex 03, France, 31076
    • Investigational Site Number 250011
  • Toulouse Cedex 09, France, 31052
    • Investigational Site Number 250003
• Germany
  • Aachen, Germany, 52074
    • Investigational Site Number 276003
  • Dresden, Germany, 01307
    • Investigational Site Number 276007
  • Düsseldorf, Germany, 40225
    • Investigational Site Number 276004
  • Erlangen, Germany, 91054
    • Investigational Site Number 276001
  • Hamburg, Germany, 20246
    • Investigational Site Number 276011
  • Hamburg, Germany, 22399
    • Investigational Site Number 276005
  • Homburg, Germany, 66421
    • Investigational Site Number 276010
  • München, Germany, 81675
    • Investigational Site Number 276006
  • Nürtingen, Germany, 72622
    • Investigational Site Number 276012
  • Tübingen, Germany, 72076
    • Investigational Site Number 276008
  • Wuppertal, Germany, 42103
    • Investigational Site Number 276002
• Hungary
  • Budapest, Hungary, 1122
    • Investigational Site Number 348001
  • Budapest, Hungary, 1134
    • Investigational Site Number 348005
  • Budapest, Hungary, 1145
    • Investigational Site Number 348004
  • Miskolc, Hungary, 3526
    • Investigational Site Number 348006
  • Pécs, Hungary, 7624
    • Investigational Site Number 348003
• Korea, Republic of
  • Seongnam, Korea, Republic of, 463-707
    • Investigational Site Number 410003
  • Seoul, Korea, Republic of, 110-744
    • Investigational Site Number 410002
  • Seoul, Korea, Republic of, 120-752
    • Investigational Site Number 410004
  • Seoul, Korea, Republic of, 138-736
    • Investigational Site Number 410001
  • Seoul, Korea, Republic of, 135-710
    • Investigational Site Number 410005
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Investigational Site Number 528005
  • Blaricum, Netherlands, 1261 AN
    • Investigational Site Number 528003
  • Hoofddorp, Netherlands, 2134 TM
    • Investigational Site Number 528004
  • Nijmegen, Netherlands, 6525 GA
    • Investigational Site Number 528002
  • Zwolle, Netherlands, 8025 AB
    • Investigational Site Number 528001
• Peru
  • Arequipa, Peru, 5154
    • Investigational Site Number 604003
  • Lima, Peru, Lima 41
    • Investigational Site Number 604005
  • Lima, Peru, 027
    • Investigational Site Number 604006
  • Lima, Peru, 041
    • Investigational Site Number 604001
  • Lima, Peru, LIM27
    • Investigational Site Number 604007
  • Lima, Peru, Lima -41
    • Investigational Site Number 604002
  • Lima, Peru, LIMA 01
    • Investigational Site Number 604004
• Poland
  • Lubin, Poland, 59-300
    • Investigational Site Number 616006
  • Olsztyn, Poland, 10-228
    • Investigational Site Number 616002
  • Rybnik, Poland, 44-200
    • Investigational Site Number 616001
  • Siedlce, Poland, 08-110
    • Investigational Site Number 616005
  • Torun, Poland, 87-100
    • Investigational Site Number 616004
• Romania
  • Alba Iulia, Romania, 510077
    • Investigational Site Number 642005
  • Baia Mare, Romania, 430031
    • Investigational Site Number 642006
  • Bucuresti, Romania, 010976
    • Investigational Site Number 642009
  • Bucuresti, Romania, 022328
    • Investigational Site Number 642008
  • Cluj Napoca, Romania, 400015
    • Investigational Site Number 642001
  • Cluj Napoca, Romania, 400015
    • Investigational Site Number 642003
  • Cluj Napoca, Romania, 400015
    • Investigational Site Number 642004
  • Cluj Napoca, Romania, 400058
    • Investigational Site Number 642002
  • Focsani, Romania, 620034
    • Investigational Site Number 642012
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642007
  • Onesti, Romania, 601048
    • Investigational Site Number 642013
• Russian Federation
  • Ekaterinburg, Russian Federation, 620036
    • Investigational Site Number 643009
  • Moscow, Russian Federation, 105425
    • Investigational Site Number 643007
  • Moscow, Russian Federation, 115478
    • Investigational Site Number 643005
  • Moscow, Russian Federation, 117997
    • Investigational Site Number 643004
  • Moscow, Russian Federation, 125284
    • Investigational Site Number 643006
  • Obninsk, Russian Federation, 249036
    • Investigational Site Number 643008
  • St.Petersburg, Russian Federation, 197022
    • Investigational Site Number 643001
  • St.Petersburg, Russian Federation, 197758
    • Investigational Site Number 643010
  • Tula, Russian Federation, 300053
    • Investigational Site Number 643003
• South Africa
  • Cape Town, South Africa, 7570
    • Investigational Site Number 710003
  • Durban, South Africa, 4001
    • Investigational Site Number 710002
  • Johannesburg, South Africa, 2193
    • Investigational Site Number 710005
  • Johannesburg, South Africa, 2196
    • Investigational Site Number 710004
  • Pretoria, South Africa, 0001
    • Investigational Site Number 710001
• Spain
  • Badalona, Spain, 08916
    • Investigational Site Number 724003
  • Barcelona, Spain, 08035
    • Investigational Site Number 724001
  • Madrid, Spain, 28033
    • Investigational Site Number 724002
  • Madrid, Spain, 28050
    • Investigational Site Number 724008
  • Málaga, Spain, 29010
    • Investigational Site Number 724006
  • Palma De Mallorca, Spain, 07010
    • Investigational Site Number 724005
  • Sabadell, Spain, 08208
    • Investigational Site Number 724004
  • Sevilla, Spain, 41071
    • Investigational Site Number 724007
• Taiwan
  • Taiching, Taiwan, 40447
    • Investigational Site Number 158002
  • Tainan, Taiwan, 704
    • Investigational Site Number 158003
  • Taipei, Taiwan, 100
    • Investigational Site Number 158001
• Tunisia
  • Sfax, Tunisia, 3029
    • Investigational Site Number 788004
  • Sousse, Tunisia, 4000
    • Investigational Site Number 788003
  • Tunis, Tunisia, 1006
    • Investigational Site Number 788002
• Turkey
  • Antalya, Turkey, 07059
    • Investigational Site Number 792003
  • Bornova, Turkey, 35100
    • Investigational Site Number 792001
  • Istanbul, Turkey, 34093
    • Investigational Site Number 792002
• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Investigational Site Number 826002
  • Colchester, United Kingdom, CO3 3NB
    • Investigational Site Number 826004
  • Glasgow, United Kingdom, G11 6NT
    • Investigational Site Number 826005
  • Guildford, United Kingdom, GU2 7XX
    • Investigational Site Number 826006
  • Manchester, United Kingdom, M20 4BX
    • Investigational Site Number 826007
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Investigational Site Number 826003
  • Sutton, United Kingdom, SM2 5PT
    • Investigational Site Number 826001
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35661
      • Investigational Site Number 840002
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Investigational Site Number 840004
  • California
    • Anaheim, California, United States, 92801
      • Investigational Site Number 840008
    • La Jolla, California, United States, 92093
      • Investigational Site Number 840010
    • San Bernardino, California, United States, 92404
      • Investigational Site Number 840001
  • Connecticut
    • Stamford, Connecticut, United States, 06902
      • Investigational Site Number 840021
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Investigational Site Number 840023
    • Lakeland, Florida, United States, 33805
      • Investigational Site Number 840013
    • Port St. Lucie, Florida, United States, 34952
      • Investigational Site Number 840003
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Investigational Site Number 840007
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Investigational Site Number 840014
    • Rockville, Maryland, United States, 20850
      • Investigational Site Number 840005
  • Minnesota
    • St Louis Park, Minnesota, United States, 55416
      • Investigational Site Number 840017
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Investigational Site Number 840011
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Investigational Site Number 840016
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Investigational Site Number 840015
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Investigational Site Number 840024
  • Ohio
    • Akron, Ohio, United States, 44302
      • Investigational Site Number 840020
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Investigational Site Number 840006
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Investigational Site Number 840025
  • Texas
    • Corpus Christi, Texas, United States, 78405
      • Investigational Site Number 840012

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. Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that was resistant to hormone therapy and previously treated with a docetaxel-containing regimen.

I 02. Participant must had either measurable or non-measurable disease. I 03. Received prior castration by orchiectomy and/or Luteinizing Hormone-Releasing Hormone (LH-RH) agonist with or without antiandrogen, antiandrogen withdrawal, monotherapy with estramustine, or other hormonal agents.

I 04. Life expectancy > 6 months. I 05. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2 (i.e, participant must be ambulatory, capable of all self-care, and up and about more than 50% of waking hours).

I 06. Age ≥18 years (or country's legal age of majority if the legal age was > 18 years).

Exclusion criteria:

E 01. Previous treatment with mitoxantrone or cabazitaxel. E 02. Prior isotope therapy or radiotherapy to ≥30% of bone marrow. In case of prior isotope therapy 12 weeks must had elapsed prior to first study drug administration.

E 03. 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 04. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study.

E 05. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥ 5 years ago and from which the participant had been disease-free for ≥ 5 years.

E 06. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.

E 07. Known brain or leptomeningeal involvement. E 08. Other concurrent serious illness or medical conditions. E 09. Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of congestive heart failure (NYHA III or IV) or myocardial infarction within last 6 months was also not allowed.

E 10. Any severe acute or chronic medical condition which could impair the ability of the participant to participate to the study or to comply with the study procedures or interfere with interpretation of study results.

E 11. Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent form prior to enrollment into the study.

E 12. Participants with reproductive potential who did not agree to use accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" was based on the Investigator's judgment. Participant's Partners of childbearing potential (unless surgically sterile, post menopausal or for another reason had no chance of becoming pregnant) not protected by highly effective contraceptive method of birth control as defined for contraception in the Informed Consent Form and /or in a local protocol addendum.

E 13. History of hypersensitivity to docetaxel, or polysorbate 80. E 14. Inadequate organ and bone marrow function. E 15. Contraindications to the use of corticosteroid treatment. E 16. Symptomatic peripheral neuropathy grade > 2 (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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cabazitaxel 20 mg/m^2; Cabazitaxel 20 mg/m^2 intravenous (IV) infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Drug: Cabazitaxel (XRP6258); Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous; Other Names: Jevtana®; Drug: Prednisone (or Prednisolone); Pharmaceutical form: Tablet Route of administration: Oral
EXPERIMENTAL: Cabazitaxel 25 mg/m^2; Cabazitaxel 25 mg/m^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Drug: Cabazitaxel (XRP6258); Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous; Other Names: Jevtana®; Drug: Prednisone (or Prednisolone); Pharmaceutical form: Tablet Route of administration: Oral

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 absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive or the study cut-off date. The cut-off date for the final analysis of OS was the date when the 988th death had been observed. Analysis was performed by Kaplan-Meier method.	From baseline up to death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was evaluated from date of randomization to date of first documentation of any of the events: 1) Radiological tumor progression: as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target lesions, 2) Prostate Specific Antigen (PSA) progression: ≥25% increase over baseline/nadir value if baseline PSA ≥10 ng/mL; or 25% increase above the baseline level if baseline PSA >0 ng/mL & <10 ng/mL; or post-baseline value of >=2 ng/mL, if baseline PSA=0 ng/mL, 3) Pain progression: increase of ≥1 point in median Present Pain Intensity (PPI) from nadir or ≥25% increase in mean analgesic score (AS) from baseline score or requirement of local palliative radiotherapy, 4) Death. Analysis was performed by Kaplan-Meier method.	From baseline up to tumor progression, PSA progression, pain progression, death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
Time to Tumor Progression	Time to Tumor progression was defined as the first occurrence of radiological tumor progression according to RECIST 1.1. Radiological tumor progression was defined at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target-lesions. Analysis was performed by Kaplan-Meier method.	From baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
Percentage of Participants With Overall Objective Tumor Response	Overall objective tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1 criteria, as assessed by the investigator. 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 had 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.	From baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
Time to PSA Progression	Time to PSA progression was time interval between randomization & first occurrence of PSA progression. PSA progression defined as: 1) PSA responders (>50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over nadir value, confirmed by second PSA ≥3 weeks later; 2) PSA non-responders (did not achieve >50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over baseline value, confirmed by second PSA ≥3 weeks later; 3) In participants not eligible for PSA response (baseline PSA <10 ng/mL): (a) participants with baseline PSA >0 ng/mL & <10 ng/mL: increase in PSA by 25% (≥2 ng/mL) above baseline level, confirmed by second PSA value ≥3 weeks apart; (b) participants with baseline value=0 ng/mL: post-baseline PSA value ≥2 ng/mL. Note (for 1-3): Rise in PSA in first 12 weeks was progression only if met definition above and was associated with other sign of DP or if it continued beyond 12 weeks. Analysis was performed by Kaplan-Meier method.	From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 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.	From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
Time to Pain Progression	Pain Progression was defined as an increase of ≥1 point in the median PPI from its nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean AS compared with the baseline score 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. AS 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.	From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 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 AS, or a ≥50% decrease from baseline mean AS without increase in the PPI score, maintained for 2 consecutive evaluations at least 3 weeks apart. Increases in pain during the first 12 weeks were ignored in determining pain response.	From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL)	FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists 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 TOI combines physical well-being, functional well-being, and prostate-specific concerns sub-scales for a total possible score range of 0 to 104, where higher values represent better HRQoL.	Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks)
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL	FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists 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 sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL.	Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks)
Percentage of Participants With FACT-P Total Score Response	FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists 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 sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL. Responder of FACT-P was defined as at least one occurrence of 7-point improvement from baseline in FACT-P total score during treatment period.	From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales	The time to definitive deterioration (10% decrease in score from baseline) was assessed for the individual sub-scales (Physical Well-Being; Social/Family Well-Being; Emotional Well-Being; Functional Well-Being; Prostate-Specific Concerns). Analysis was performed by Kaplan-Meier method.	From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
Time to Definitive Deterioration of ECOG PS Score From Baseline	The ECOG PS was used to evaluate participant's DP and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for < 50 % of the time; 3= in bed for > 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG PS score from baseline was defined as a change from 0, 1 to ≥2, or from 2 to ≥3. Analysis was performed by Kaplan-Meier method.	From baseline until death or study cut-off date (maximum duration: 48 months)
Time to Definitive Weight Loss by 5% and 10% From Baseline	Time to definitive weight loss was defined as the time to first occurrence of ≥5% or ≥10% decrease in body weight from baseline. Analysis was performed by Kaplan-Meier method.	From baseline until death or study cut-off date (maximum duration: 48 months)
Time to First Definitive Consumption of Narcotic Medication	Concomitant medications used were recorded for all participants, and time of first definitive consumption of narcotic medication (if it occurred) was determined. This measure summarizes the time from baseline to first definitive consumption of narcotic medication. Analysis was performed by Kaplan-Meier method.	From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during on-treatment period. On-treatment period: The time from the first dose of treatment to 30 days after the last dose of treatment (either Cabazitaxel or Prednisone). A serious adverse event: Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 4.03 (Grade 3 [severe] and Grade 4 [life-threatening]) was used in this study to grade clinical AEs.	From first administration of study treatment until 30 days after the last administration of study treatment (Maximum duration: 48 months)
Plasma Clearance (CL) for Cabazitaxel	Blood samples for pharmacokinetic (PK) analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.	Day 1 of Cycle 1: 5 minutes before the end of infusion (EOI), 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI
Plasma Steady State Volume of Distribution (Vss) for Cabazitaxel	Blood samples for PK analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.	Day 1 of Cycle 1: 5 minutes before the EOI, 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI

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.
• Meisel A, de Wit R, Oudard S, Sartor O, Stenner-Liewen F, Shun Z, Foster M, Ozatilgan A, Eisenberger M, de Bono JS. Neutropenia, neutrophilia, and neutrophil-lymphocyte ratio as prognostic markers in patients with metastatic castration-resistant prostate cancer. Ther Adv Med Oncol. 2022 Jun 1;14:17588359221100022. doi: 10.1177/17588359221100022. eCollection 2022.
• Eisenberger M, Hardy-Bessard AC, Kim CS, Geczi L, Ford D, Mourey L, Carles J, Parente P, Font A, Kacso G, Chadjaa M, Zhang W, Bernard J, de Bono J. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206. doi: 10.1200/JCO.2016.72.1076. Epub 2017 Aug 15.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2015

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): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: August 1, 2016

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; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone; Prednisone
• Other Study ID Numbers: EFC11785; 2010-022163-35 (EUDRACT_NUMBER)