Clinical trial NCT01308567: Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 1168
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months )
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)
measure: Time to Tumor Progression Free Survival
timeFrame: Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
measure: Percentage of Participants With Overall Objective Tumor Response
timeFrame: Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
measure: Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS)
timeFrame: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
measure: Percentage of Participants With PSA Response
timeFrame: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
measure: Time to Pain Progression Free Survival (Pain PFS)
timeFrame: Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)
measure: Percentage of Participants With Pain Response
timeFrame: Baseline until pain progression, death or study cut-off date (maximum duration: 51 months)
measure: Skeletal Related Events (SRE) Free Survival
timeFrame: Baseline until occurrence of first SRE or death (maximum duration: 51 months)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL)
timeFrame: 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)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL
timeFrame: 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)
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Investigational Site Number 840004
state: Alabama
city: Anaheim
country: United States
facility: Investigational Site Number 840009
state: California
city: Bakersfield
country: United States
facility: Investigational Site Number 840014
state: California
city: Sacramento
country: United States
facility: Investigational Site Number 840030
state: California
city: San Bernardino
country: United States
facility: Investigational Site Number 840003
state: California
city: San Francisco
country: United States
facility: Investigational Site Number 840012
state: California
city: Denver
country: United States
facility: Investigational Site Number 840019
state: Colorado
city: Boca Raton
country: United States
facility: Investigational Site Number 840013
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840035
state: Florida
city: Port Saint Lucie
country: United States
facility: Investigational Site Number 840001
state: Florida
city: Decatur
country: United States
facility: Investigational Site Number 840015
state: Illinois
city: Wichita
country: United States
facility: Investigational Site Number 840018
state: Kansas
city: Paducah
country: United States
facility: Investigational Site Number 840010
state: Kentucky
city: New Orleans
country: United States
facility: Investigational Site Number 840008
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 840006
state: Maryland
city: Boston
country: United States
facility: Investigational Site Number 840238
state: Massachusetts
city: Boston
country: United States
facility: Investigational Site Number 840138
state: Massachusetts
city: Brookline
country: United States
facility: Investigational Site Number 840038
state: Massachusetts
city: Detroit
country: United States
facility: Investigational Site Number 840005
state: Michigan
city: Saint Louis Park
country: United States
facility: Investigational Site Number 840021
state: Minnesota
city: Kansas City
country: United States
facility: Investigational Site Number 840016
state: Missouri
city: Lincoln
country: United States
facility: Investigational Site Number 840020
state: Nebraska
city: East Orange
country: United States
facility: Investigational Site Number 840017
state: New Jersey
city: Albuquerque
country: United States
facility: Investigational Site Number 840033
state: New Mexico
city: Raleigh
country: United States
facility: Investigational Site Number 840036
state: North Carolina
city: Washington
country: United States
facility: Investigational Site Number 840011
state: North Carolina
city: Akron
country: United States
facility: Investigational Site Number 840026
state: Ohio
city: Cleveland
country: United States
facility: Investigational Site Number 840023
state: Ohio
city: Dunmore
country: United States
facility: Investigational Site Number 840032
state: Pennsylvania
city: Pawtucket
country: United States
facility: Investigational Site Number 840007
state: Rhode Island
city: Myrtle Beach
country: United States
facility: Investigational Site Number 840037
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 840028
state: Tennessee
city: Bankstown
country: Australia
facility: Investigational Site Number 036016
city: Camperdown
country: Australia
facility: Investigational Site Number 036008
city: Coffs Harbour
country: Australia
facility: Investigational Site Number 036015
city: Concord
country: Australia
facility: Investigational Site Number 036001
city: Fitzroy
country: Australia
facility: Investigational Site Number 036017
city: Herston
country: Australia
facility: Investigational Site Number 036003
city: Hornsby
country: Australia
facility: Investigational Site Number 036010
city: Kurralta Park
country: Australia
facility: Investigational Site Number 036012
city: Parkville
country: Australia
facility: Investigational Site Number 036002
city: South Brisbane
country: Australia
facility: Investigational Site Number 036009
city: Subiaco
country: Australia
facility: Investigational Site Number 036011
city: Wodonga
country: Australia
facility: Investigational Site Number 036013
city: Minsk
country: Belarus
facility: Investigational Site Number 112001
city: Minsk
country: Belarus
facility: Investigational Site Number 112002
city: Vitebsk
country: Belarus
facility: Investigational Site Number 112004
city: Passo Fundo
country: Brazil
facility: Investigational Site Number 076006
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076002
city: Rio De Janeiro
country: Brazil
facility: Investigational Site Number 076004
city: Sao Jose Do Rio Preto
country: Brazil
facility: Investigational Site Number 076009
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076005
city: Uberlandia
country: Brazil
facility: Investigational Site Number 076003
city: London
country: Canada
facility: Investigational Site Number 124002
city: Mississauga
country: Canada
facility: Investigational Site Number 124007
city: Moncton
country: Canada
facility: Investigational Site Number 124005
city: Montreal
country: Canada
facility: Investigational Site Number 124003
city: Quebec
country: Canada
facility: Investigational Site Number 124004
city: Toronto
country: Canada
facility: Investigational Site Number 124006
city: Beijing
country: China
facility: Investigational Site Number 156005
city: Shanghai
country: China
facility: Investigational Site Number 156002
city: Shanghai
country: China
facility: Investigational Site Number 156003
city: Shanghai
country: China
facility: Investigational Site Number 156004
city: Brno
country: Czechia
facility: Investigational Site Number 203002
city: Novy Jicin
country: Czechia
facility: Investigational Site Number 203003
city: Olomouc
country: Czechia
facility: Investigational Site Number 203001
city: Praha 2
country: Czechia
facility: Investigational Site Number 203004
city: Herlev
country: Denmark
facility: Investigational Site Number 208002
city: København Ø
country: Denmark
facility: Investigational Site Number 208001
city: Odense C
country: Denmark
facility: Investigational Site Number 208003
city: Ålborg
country: Denmark
facility: Investigational Site Number 208004
city: Helsinki
country: Finland
facility: Investigational Site Number 246002
city: Kuopio
country: Finland
facility: Investigational Site Number 246001
city: Turku
country: Finland
facility: Investigational Site Number 246003
city: Besancon Cedex
country: France
facility: Investigational Site Number 250010
city: Bordeaux Cedex
country: France
facility: Investigational Site Number 250002
city: Caen Cedex 05
country: France
facility: Investigational Site Number 250006
city: Lyon
country: France
facility: Investigational Site Number 250005
city: Paris Cedex 05
country: France
facility: Investigational Site Number 250003
city: Paris Cedex 10
country: France
facility: Investigational Site Number 250004
city: Paris Cedex 15
country: France
facility: Investigational Site Number 250001
city: Poitiers Cedex
country: France
facility: Investigational Site Number 250007
city: Suresnes
country: France
facility: Investigational Site Number 250008
city: Villejuif
country: France
facility: Investigational Site Number 250009
city: Aachen
country: Germany
facility: Investigational Site Number 276003
city: Berlin
country: Germany
facility: Investigational Site Number 276005
city: Düsseldorf
country: Germany
facility: Investigational Site Number 276001
city: Erlangen
country: Germany
facility: Investigational Site Number 276004
city: Homburg
country: Germany
facility: Investigational Site Number 276002
city: München
country: Germany
facility: Investigational Site Number 276006
city: Kfar Saba
country: Israel
facility: Investigational Site Number 376004
city: Petah-Tikva
country: Israel
facility: Investigational Site Number 376003
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376002
city: Arezzo
country: Italy
facility: Investigational Site Number 380001
city: Bari
country: Italy
facility: Investigational Site Number 380004
city: Orbassano
country: Italy
facility: Investigational Site Number 380003
city: Roma
country: Italy
facility: Investigational Site Number 380005
city: Trento
country: Italy
facility: Investigational Site Number 380002
city: Bunkyo-Ku
country: Japan
facility: Investigational Site Number 392001
city: Chiba-Shi
country: Japan
facility: Investigational Site Number 392003
city: Kashiwa-Shi
country: Japan
facility: Investigational Site Number 392006
city: Koto-Ku
country: Japan
facility: Investigational Site Number 392005
city: Osaka Sayama-Shi
country: Japan
facility: Investigational Site Number 392002
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392004
city: Acapulco
country: Mexico
facility: Investigational Site Number 484007
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 484008
city: D.f.
country: Mexico
facility: Investigational Site Number 484003
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484004
city: Merida
country: Mexico
facility: Investigational Site Number 484009
city: Queretaro
country: Mexico
facility: Investigational Site Number 484005
city: San Luis Potosi
country: Mexico
facility: Investigational Site Number 484002
city: Zapopan
country: Mexico
facility: Investigational Site Number 484006
city: Lima
country: Peru
facility: Investigational Site Number 604006
city: Lima
country: Peru
facility: Investigational Site Number 604001
city: Lima
country: Peru
facility: Investigational Site Number 604005
city: Lima
country: Peru
facility: Investigational Site Number 604002
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616002
city: Gdansk
country: Poland
facility: Investigational Site Number 616001
city: Koscierzyna
country: Poland
facility: Investigational Site Number 616003
city: Lodz
country: Poland
facility: Investigational Site Number 616005
city: Poznan
country: Poland
facility: Investigational Site Number 616004
city: Coimbra
country: Portugal
facility: Investigational Site Number 620003
city: Lisboa
country: Portugal
facility: Investigational Site Number 620005
city: Lisboa
country: Portugal
facility: Investigational Site Number 620004
city: Porto
country: Portugal
facility: Investigational Site Number 620001
city: Porto
country: Portugal
facility: Investigational Site Number 620002
city: Baia Mare
country: Romania
facility: Investigational Site Number 642004
city: Bucharest
country: Romania
facility: Investigational Site Number 642008
city: Bucuresti
country: Romania
facility: Investigational Site Number 642005
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642002
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642003
city: Hunedoara
country: Romania
facility: Investigational Site Number 642007
city: Ekaterinburg
country: Russian Federation
facility: Investigational Site Number 643004
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643008
city: Omsk
country: Russian Federation
facility: Investigational Site Number 643003
city: Pyatigorsk
country: Russian Federation
facility: Investigational Site Number 643002
city: Ryazan
country: Russian Federation
facility: Investigational Site Number 643007
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643005
city: Tomsk
country: Russian Federation
facility: Investigational Site Number 643001
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643006
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Barcelona
country: Spain
facility: Investigational Site Number 724007
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Hospitalet De Llobregat
country: Spain
facility: Investigational Site Number 724003
city: Madrid
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724004
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724006
city: Malmö
country: Sweden
facility: Investigational Site Number 752003
city: Stockholm
country: Sweden
facility: Investigational Site Number 752002
city: Uppsala
country: Sweden
facility: Investigational Site Number 752001
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number 158004
city: Taichung
country: Taiwan
facility: Investigational Site Number 158002
city: Taipei
country: Taiwan
facility: Investigational Site Number 158001
city: Tao-Yuan
country: Taiwan
facility: Investigational Site Number 158003
city: Ankara
country: Turkey
facility: Investigational Site Number 792002
city: Istanbul
country: Turkey
facility: Investigational Site Number 792001
city: Cherkasy
country: Ukraine
facility: Investigational Site Number 804009
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number 804004
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804010
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 804006
city: Kharkov
country: Ukraine
facility: Investigational Site Number 804003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804002
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804001
city: Lutsk
country: Ukraine
facility: Investigational Site Number 804007
city: Uzhgorod
country: Ukraine
facility: Investigational Site Number 804005
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number 804008
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Oudard S, Fizazi K, Sengelov L, Daugaard G, Saad F, Hansen S, Hjalm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O. Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. doi: 10.1200/JCO.2016.72.1068. Epub 2017 Jul 28.
citation: de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.
citation: Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.