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

NCT01308567 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC117842010-022064-12U1111-1117-8356
• Study Type: interventional
• Target: 1,168
• Locations: 25 countries
• Sites: 167

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Progression Free Survival (PFS)

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

• 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)

• 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)

• 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)

• 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)

Study Arms (3)

Cabazitaxel 25 mg/m^2

EXPERIMENTAL

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); Drug: Prednisone

Cabazitaxel 20 mg/m^2

EXPERIMENTAL

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); Drug: Prednisone

Docetaxel 75 mg/m^2

ACTIVE COMPARATOR

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: Docetaxel (XRP6976); Drug: Prednisone

Interventions

Cabazitaxel (XRP6258) DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

Cabazitaxel 20 mg/m^2; Cabazitaxel 25 mg/m^2

Docetaxel (XRP6976) DRUG

Pharmaceutical form: Solution for injection'; Route of administration: Intravenous

Docetaxel 75 mg/m^2

Prednisone DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Cabazitaxel 20 mg/m^2; Cabazitaxel 25 mg/m^2; Docetaxel 75 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (167)

Investigational Site Number 840004

Muscle Shoals, Alabama, 35661, United States

Location

Investigational Site Number 840009

Anaheim, California, 92801, United States

Location

Investigational Site Number 840014

Bakersfield, California, 93309, United States

Location

Investigational Site Number 840030

Sacramento, California, 95816, United States

Location

Investigational Site Number 840003

San Bernardino, California, 92404, United States

Location

Investigational Site Number 840012

San Francisco, California, 94143, United States

Location

Investigational Site Number 840019

Denver, Colorado, 80262, United States

Location

Investigational Site Number 840013

Boca Raton, Florida, 33486, United States

Location

Investigational Site Number 840035

Jacksonville, Florida, 32256, United States

Location

Investigational Site Number 840001

Port Saint Lucie, Florida, 34952, United States

Location

Investigational Site Number 840015

Decatur, Illinois, 62526, United States

Location

Investigational Site Number 840018

Wichita, Kansas, 67214, United States

Location

Investigational Site Number 840010

Paducah, Kentucky, 42002, United States

Location

Investigational Site Number 840008

New Orleans, Louisiana, 70112, United States

Location

Investigational Site Number 840006

Rockville, Maryland, 20850, United States

Location

Investigational Site Number 840238

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 840138

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840038

Brookline, Massachusetts, 02115, United States

Location

Investigational Site Number 840005

Detroit, Michigan, 48202, United States

Location

Investigational Site Number 840021

Saint Louis Park, Minnesota, 55416, United States

Location

Investigational Site Number 840016

Kansas City, Missouri, 64128, United States

Location

Investigational Site Number 840020

Lincoln, Nebraska, 68506, United States

Location

Investigational Site Number 840017

East Orange, New Jersey, 07018, United States

Location

Investigational Site Number 840033

Albuquerque, New Mexico, 87109, United States

Location

Investigational Site Number 840036

Raleigh, North Carolina, 27607, United States

Location

Investigational Site Number 840011

Washington, North Carolina, 27889, United States

Location

Investigational Site Number 840026

Akron, Ohio, 44302, United States

Location

Investigational Site Number 840023

Cleveland, Ohio, 44106, United States

Location

Investigational Site Number 840032

Dunmore, Pennsylvania, 18512, United States

Location

Investigational Site Number 840007

Pawtucket, Rhode Island, 02860, United States

Location

Investigational Site Number 840037

Myrtle Beach, South Carolina, 29572, United States

Location

Investigational Site Number 840028

Chattanooga, Tennessee, 37421, United States

Location

Investigational Site Number 036016

Bankstown, 2200, Australia

Location

Investigational Site Number 036008

Camperdown, 2050, Australia

Location

Investigational Site Number 036015

Coffs Harbour, 2450, Australia

Location

Investigational Site Number 036001

Concord, 2137, Australia

Location

Investigational Site Number 036017

Fitzroy, 3065, Australia

Location

Investigational Site Number 036003

Herston, 4029, Australia

Location

Investigational Site Number 036010

Hornsby, 2077, Australia

Location

Investigational Site Number 036012

Kurralta Park, 5037, Australia

Location

Investigational Site Number 036002

Parkville, 3050, Australia

Location

Investigational Site Number 036009

South Brisbane, 4101, Australia

Location

Investigational Site Number 036011

Subiaco, 6008, Australia

Location

Investigational Site Number 036013

Wodonga, 3690, Australia

Location

Investigational Site Number 112001

Minsk, 220013, Belarus

Location

Investigational Site Number 112002

Minsk, 223040, Belarus

Location

Investigational Site Number 112004

Vitebsk, 210603, Belarus

Location

Investigational Site Number 076006

Passo Fundo, 99010-260, Brazil

Location

Investigational Site Number 076001

Porto Alegre, 90035-001, Brazil

Location

Investigational Site Number 076002

Porto Alegre, 90610-000, Brazil

Location

Investigational Site Number 076004

Rio de Janeiro, 20230-130, Brazil

Location

Investigational Site Number 076009

São José do Rio Preto, 15090-000, Brazil

Location

Investigational Site Number 076005

São Paulo, 01246-000, Brazil

Location

Investigational Site Number 076003

Uberlândia, 38408 150, Brazil

Location

Investigational Site Number 124002

London, N6A 4L6, Canada

Location

Investigational Site Number 124007

Mississauga, L5M 2N1, Canada

Location

Investigational Site Number 124005

Moncton, E1C 6Z8, Canada

Location

Investigational Site Number 124003

Montreal, H2L 4M1, Canada

Location

Investigational Site Number 124004

Québec, G1R 2J6, Canada

Location

Investigational Site Number 124006

Toronto, M4N 3M5, Canada

Location

Investigational Site Number 156005

Beijing, 100034, China

Location

Investigational Site Number 156002

Shanghai, 200032, China

Location

Investigational Site Number 156003

Shanghai, 200040, China

Location

Investigational Site Number 156004

Shanghai, 200040, China

Location

Investigational Site Number 203002

Brno, 65653, Czechia

Location

Investigational Site Number 203003

Nový Jičín, 74101, Czechia

Location

Investigational Site Number 203001

Olomouc, 77520, Czechia

Location

Investigational Site Number 203004

Prague, 12808, Czechia

Location

Investigational Site Number 208004

Aalborg, 9100, Denmark

Location

Investigational Site Number 208002

Herlev, 2730, Denmark

Location

Investigational Site Number 208001

København Ø, 2100, Denmark

Location

Investigational Site Number 208003

Odense C, 5000, Denmark

Location

Investigational Site Number 246002

Helsinki, 00290, Finland

Location

Investigational Site Number 246001

Kuopio, 70210, Finland

Location

Investigational Site Number 246003

Turku, FIN-20520, Finland

Location

Investigational Site Number 250010

Besançon, 25030, France

Location

Investigational Site Number 250002

Bordeaux, 33076, France

Location

Investigational Site Number 250006

Caen, 14076, France

Location

Investigational Site Number 250005

Lyon, 69373, France

Location

Investigational Site Number 250003

Paris, 75231, France

Location

Investigational Site Number 250004

Paris, 75475, France

Location

Investigational Site Number 250001

Paris, 75908, France

Location

Investigational Site Number 250007

Poitiers, 86021, France

Location

Investigational Site Number 250008

Suresnes, 92151, France

Location

Investigational Site Number 250009

Villejuif, 94805, France

Location

Investigational Site Number 276003

Aachen, 52074, Germany

Location

Investigational Site Number 276005

Berlin, 14197, Germany

Location

Investigational Site Number 276001

Düsseldorf, 40225, Germany

Location

Investigational Site Number 276004

Erlangen, 91054, Germany

Location

Investigational Site Number 276002

Homburg, 66421, Germany

Location

Investigational Site Number 276006

München, 81675, Germany

Location

Investigational Site Number 376004

Kfar Saba, 44281, Israel

Location

Investigational Site Number 376003

Petah Tikva, 49100, Israel

Location

Investigational Site Number 376002

Tel Aviv, 64239, Israel

Location

Investigational Site Number 380001

Arezzo, 06156, Italy

Location

Investigational Site Number 380004

Bari, 70124, Italy

Location

Investigational Site Number 380003

Orbassano, 10043, Italy

Location

Investigational Site Number 380005

Roma, 00144, Italy

Location

Investigational Site Number 380002

Trento, 38100, Italy

Location

Investigational Site Number 392001

Bunkyō City, Japan

Location

Investigational Site Number 392003

Chiba, Japan

Location

Investigational Site Number 392006

Kashiwa-Shi, Japan

Location

Investigational Site Number 392005

Kōtoku, Japan

Location

Investigational Site Number 392004

Osaka, Japan

Location

Investigational Site Number 392002

Osaka Sayama-Shi, Japan

Location

Investigational Site Number 484007

Acapulco, 39670, Mexico

Location

Investigational Site Number 484008

Aguascalientes, 20230, Mexico

Location

Investigational Site Number 484003

D.F., 14080, Mexico

Location

Investigational Site Number 484004

Guadalajara, 44280, Mexico

Location

Investigational Site Number 484009

Mérida, 97134, Mexico

Location

Investigational Site Number 484005

Querétaro, 76000, Mexico

Location

Investigational Site Number 484002

San Luis Potosí City, Mexico

Location

Investigational Site Number 484006

Zapopan, 45040, Mexico

Location

Investigational Site Number 604006

Lima, 027, Peru

Location

Investigational Site Number 604001

Lima, 041, Peru

Location

Investigational Site Number 604005

Lima, LIMA 01, Peru

Location

Investigational Site Number 604002

Lima, LIMA 34, Peru

Location

Investigational Site Number 616002

Bydgoszcz, 85-796, Poland

Location

Investigational Site Number 616001

Gdansk, 80-952, Poland

Location

Investigational Site Number 616003

Kościerzyna, 83-400, Poland

Location

Investigational Site Number 616005

Lodz, 93-509, Poland

Location

Investigational Site Number 616004

Poznan, 61-485, Poland

Location

Investigational Site Number 620003

Coimbra, 3049, Portugal

Location

Investigational Site Number 620005

Lisbon, 1099-023, Portugal

Location

Investigational Site Number 620004

Lisbon, 1649-035, Portugal

Location

Investigational Site Number 620001

Porto, 4200, Portugal

Location

Investigational Site Number 620002

Porto, 4200, Portugal

Location

Investigational Site Number 642004

Baia Mare, 430031, Romania

Location

Investigational Site Number 642005

Bucharest, 022328, Romania

Location

Investigational Site Number 642008

Bucharest, 022328, Romania

Location

Investigational Site Number 642002

Cluj-Napoca, 400015, Romania

Location

Investigational Site Number 642003

Cluj-Napoca, 400015, Romania

Location

Investigational Site Number 642007

Hunedoara, 331057, Romania

Location

Investigational Site Number 643008

Moscow, 129128, Russia

Location

Investigational Site Number 643003

Omsk, 644013, Russia

Location

Investigational Site Number 643002

Pyatigorsk, 357502, Russia

Location

Investigational Site Number 643007

Ryazan, 390011, Russia

Location

Investigational Site Number 643005

Saint Petersburg, 197758, Russia

Location

Investigational Site Number 643001

Tomsk, 634028, Russia

Location

Investigational Site Number 643006

Yaroslavl, 150054, Russia

Location

Investigational Site Number 643004

Yekaterinburg, 620102, Russia

Location

Investigational Site Number 724001

Barcelona, 08003, Spain

Location

Investigational Site Number 724007

Barcelona, 08025, Spain

Location

Investigational Site Number 724002

Barcelona, 08036, Spain

Location

Investigational Site Number 724003

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724005

Madrid, 28007, Spain

Location

Investigational Site Number 724004

Madrid, 28041, Spain

Location

Investigational Site Number 724006

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 752003

Malmo, 205 02, Sweden

Location

Investigational Site Number 752002

Stockholm, 171 76, Sweden

Location

Investigational Site Number 752001

Uppsala, 751 85, Sweden

Location

Investigational Site Number 158004

Kaohsiung City, 833, Taiwan

Location

Investigational Site Number 158002

Taichung, 407, Taiwan

Location

Investigational Site Number 158001

Taipei, Taiwan

Location

Investigational Site Number 158003

Taoyuan District, 333, Taiwan

Location

Investigational Site Number 792002

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 792001

Istanbul, 34303, Turkey (Türkiye)

Location

Investigational Site Number 804009

Cherkasy, 18009, Ukraine

Location

Investigational Site Number 804004

Dnipropetrovsk, 49102, Ukraine

Location

Investigational Site Number 804010

Donetsk, 83092, Ukraine

Location

Investigational Site Number 804006

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number 804003

Kharkiv, 61037, Ukraine

Location

Investigational Site Number 804002

Kyiv, 01133, Ukraine

Location

Investigational Site Number 804001

Kyiv, 1601, Ukraine

Location

Investigational Site Number 804007

Lutsk, 43018, Ukraine

Location

Investigational Site Number 804005

Uzhhorod, 88000, Ukraine

Location

Investigational Site Number 804008

Zaporizhzhya, 69040, Ukraine

Location

Related Publications (6)

• Carrot A, Oudard S, Colomban O, Fizazi K, Maillet D, Sartor O, Freyer G, You B. Prognostic Value of the Modeled Prostate-Specific Antigen KELIM Confirmation in Metastatic Castration-Resistant Prostate Cancer Treated With Taxanes in FIRSTANA. JCO Clin Cancer Inform. 2024 Feb;8:e2300208. doi: 10.1200/CCI.23.00208.

  PMID: 38364191 DERIVED

• 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.

  PMID: 33740734 DERIVED

• 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.

  PMID: 29500065 DERIVED

• 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.

  PMID: 28753384 DERIVED

• 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.

  PMID: 24722180 DERIVED

• Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.

  PMID: 23228299 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; XRP6258; Docetaxel; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2011
• First Posted: March 4, 2011
• Study Start: May 5, 2011
• Primary Completion: September 1, 2015
• Study Completion: May 1, 2018
• Last Updated: June 5, 2019
• Results First Posted: March 3, 2017

Record last verified: 2019-05

Locations

DE (6); TU (2); BE (3); CA (6); FI (3); PT (5); ES (7); PE (4); CN (4); JP (6); US (32); ME (8); SE (3); TW (4); UA (10); PL (5); RO (6); AU (12); CZ (4); IT (5); DK (4); FR (10); BR (7); IL (3); RU (8)