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

NCT01308580 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC117852010-022163-35
• Study Type: interventional
• Target: 1,200
• Locations: 21 countries
• Sites: 169

Brief Summary

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.

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 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 Outcomes (17)

• Progression Free Survival (PFS)

  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

  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

  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

  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

  From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Study Arms (2)

Cabazitaxel 20 mg/m^2

EXPERIMENTAL

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); Drug: Prednisone (or Prednisolone)

Cabazitaxel 25 mg/m^2

EXPERIMENTAL

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); Drug: Prednisone (or Prednisolone)

Interventions

Cabazitaxel (XRP6258) DRUG

Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous

Also known as: Jevtana®

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

Prednisone (or Prednisolone) DRUG

Pharmaceutical form: Tablet Route of administration: Oral

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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (172)

Investigational Site Number 840002

Muscle Shoals, Alabama, 35661, United States

Location

Investigational Site Number 840004

Hot Springs, Arkansas, 71913, United States

Location

Investigational Site Number 840008

Anaheim, California, 92801, United States

Location

Investigational Site Number 840010

La Jolla, California, 92093, United States

Location

Investigational Site Number 840001

San Bernardino, California, 92404, United States

Location

Investigational Site Number 840021

Stamford, Connecticut, 06902, United States

Location

Investigational Site Number 840023

Jacksonville, Florida, 32256, United States

Location

Investigational Site Number 840013

Lakeland, Florida, 33805, United States

Location

Investigational Site Number 840003

Port Saint Lucie, Florida, 34952, United States

Location

Investigational Site Number 840007

New Orleans, Louisiana, 70112, United States

Location

Investigational Site Number 840014

Baltimore, Maryland, 21231, United States

Location

Investigational Site Number 840005

Rockville, Maryland, 20850, United States

Location

Investigational Site Number 840017

Saint Louis Park, Minnesota, 55416, United States

Location

Investigational Site Number 840011

Jackson, Mississippi, 39202, United States

Location

Investigational Site Number 840016

Lincoln, Nebraska, 68506, United States

Location

Investigational Site Number 840015

East Orange, New Jersey, 07018, United States

Location

Investigational Site Number 840024

Raleigh, North Carolina, 27607, United States

Location

Investigational Site Number 840020

Akron, Ohio, 44302, United States

Location

Investigational Site Number 840006

Pawtucket, Rhode Island, 02860, United States

Location

Investigational Site Number 840025

Chattanooga, Tennessee, 37421, United States

Location

Investigational Site Number 840012

Corpus Christi, Texas, 78405, United States

Location

Investigational Site Number 032002

Buenos Aires, C1120AAT, Argentina

Location

Investigational Site Number 032001

Rosario, 2000, Argentina

Location

Investigational Site Number 032003

Salta, A4406CLA, Argentina

Location

Investigational Site Number 032004

Santa Fe, 3000, Argentina

Location

Investigational Site Number 036014

Adelaide, 5000, Australia

Location

Investigational Site Number 036013

Bankstown, 2200, Australia

Location

Investigational Site Number 036010

Box Hill, 3128, Australia

Location

Investigational Site Number 036012

Camperdown, 2050, Australia

Location

Investigational Site Number 036008

Coffs Harbour, 2450, Australia

Location

Investigational Site Number 036001

Concord, 2137, Australia

Location

Investigational Site Number 036015

Elizabeth Vale, 5112, Australia

Location

Investigational Site Number 036009

Fitzroy, 3065, Australia

Location

Investigational Site Number 036007

Garran, 2605, Australia

Location

Investigational Site Number 036005

Heidelberg West, 3081, Australia

Location

Investigational Site Number 036002

Malvern, 3144, Australia

Location

Investigational Site Number 036006

South Brisbane, 4101, Australia

Location

Investigational Site Number 036016

Subiaco, 6008, Australia

Location

Investigational Site Number 036003

Wahroonga, 2076, Australia

Location

Investigational Site Number 036004

Wodonga, 3690, Australia

Location

Investigational Site Number 056007

Antwerp, B-2020, Belgium

Location

Investigational Site Number 056001

Brussels, 1000, Belgium

Location

Investigational Site Number 056008

Brussels, 1090, Belgium

Location

Investigational Site Number 056002

Brussels, 1200, Belgium

Location

Investigational Site Number 056009

Charleroi, B-6000, Belgium

Location

Investigational Site Number 056003

Ghent, 9000, Belgium

Location

Investigational Site Number 056012

Godinne, B-5530, Belgium

Location

Investigational Site Number 056016

Haine-Saint-Paul, 7100, Belgium

Location

Investigational Site Number 056005

Hasselt, B-3500, Belgium

Location

Investigational Site Number 056010

Libramont, 6800, Belgium

Location

Investigational Site Number 056013

Liège, 4000, Belgium

Location

Investigational Site Number 056011

Ottignies, 1340, Belgium

Location

Investigational Site Number 056004

Roeselare, 8800, Belgium

Location

Investigational Site Number 056006

Turnhout, B-2300, Belgium

Location

Investigational Site Number 076016

Fortaleza, Brazil

Location

Investigational Site Number 076012

Ijuí, 98700 000, Brazil

Location

Investigational Site Number 076015

Mogi das Cruzes, 08730-500, Brazil

Location

Investigational Site Number 076014

Porto Alegre, 90110-270, Brazil

Location

Investigational Site Number 076010

Rio de Janeiro, 22793-080, Brazil

Location

Investigational Site Number 076007

Salvador, 41256-900, Brazil

Location

Investigational Site Number 076003

São José do Rio Preto, 15090-000, Brazil

Location

Investigational Site Number 076009

São Paulo, 01221-020, Brazil

Location

Investigational Site Number 076001

São Paulo, 01308050, Brazil

Location

Investigational Site Number 076013

São Paulo, 01321-001, Brazil

Location

Investigational Site Number 076008

São Paulo, 01509-900, Brazil

Location

Investigational Site Number 076002

São Paulo, 03102-002, Brazil

Location

Investigational Site Number 124002

Greenfield Park, J4V 2H1, Canada

Location

Investigational Site Number 124001

Oshawa, L1G 2B9, Canada

Location

Investigational Site Number 124003

Ottawa, K1H 8L6, Canada

Location

Investigational Site Number 124005

Owen Sound, N4K 2J1, Canada

Location

Investigational Site Number 152005

Santiago, 751-0009, Chile

Location

Investigational Site Number 152004

Santiago, 7510032, Chile

Location

Investigational Site Number 152002

Santiago, 8380456, Chile

Location

Investigational Site Number 152001

Viña del Mar, 2540364, Chile

Location

Investigational Site Number 250005

Avignon, 84918, France

Location

Investigational Site Number 250008

Hyères, 83400, France

Location

Investigational Site Number 250001

La Roche-sur-Yon, 85925, France

Location

Investigational Site Number 250002

Nantes, 44202, France

Location

Investigational Site Number 250004

Nîmes, 30029, France

Location

Investigational Site Number 250010

Paris, 75014, France

Location

Investigational Site Number 250009

Reims, 51056, France

Location

Investigational Site Number 250007

Reims, 51100, France

Location

Investigational Site Number 250006

Saint-Brieuc, 22015, France

Location

Investigational Site Number 250003

Toulouse, 31052, France

Location

Investigational Site Number 250011

Toulouse, 31076, France

Location

Investigational Site Number 276003

Aachen, 52074, Germany

Location

Investigational Site Number 276007

Dresden, 01307, Germany

Location

Investigational Site Number 276004

Düsseldorf, 40225, Germany

Location

Investigational Site Number 276001

Erlangen, 91054, Germany

Location

Investigational Site Number 276011

Hamburg, 20246, Germany

Location

Investigational Site Number 276005

Hamburg, 22399, Germany

Location

Investigational Site Number 276010

Homburg, 66421, Germany

Location

Investigational Site Number 276006

München, 81675, Germany

Location

Investigational Site Number 276012

Nürtingen, 72622, Germany

Location

Investigational Site Number 276008

Tübingen, 72076, Germany

Location

Investigational Site Number 276002

Wuppertal, 42103, Germany

Location

Investigational Site Number 348001

Budapest, 1122, Hungary

Location

Investigational Site Number 348005

Budapest, 1134, Hungary

Location

Investigational Site Number 348004

Budapest, 1145, Hungary

Location

Investigational Site Number 348006

Miskolc, 3526, Hungary

Location

Investigational Site Number 348003

Pécs, 7624, Hungary

Location

Investigational Site Number 528005

Arnhem, 6815 AD, Netherlands

Location

Investigational Site Number 528003

Blaricum, 1261 AN, Netherlands

Location

Investigational Site Number 528004

Hoofddorp, 2134 TM, Netherlands

Location

Investigational Site Number 528002

Nijmegen, 6525 GA, Netherlands

Location

Investigational Site Number 528001

Zwolle, 8025 AB, Netherlands

Location

Investigational Site Number 604003

Arequipa, 5154, Peru

Location

Investigational Site Number 604006

Lima, 027, Peru

Location

Investigational Site Number 604001

Lima, 041, Peru

Location

Investigational Site Number 604007

Lima, LIM27, Peru

Location

Investigational Site Number 604002

Lima, Lima -41, Peru

Location

Investigational Site Number 604004

Lima, LIMA 01, Peru

Location

Investigational Site Number 604005

Lima, Lima 41, Peru

Location

Investigational Site Number 616006

Lubin, 59-300, Poland

Location

Investigational Site Number 616002

Olsztyn, 10-228, Poland

Location

Investigational Site Number 616001

Rybnik, 44-200, Poland

Location

Investigational Site Number 616005

Siedlce, 08-110, Poland

Location

Investigational Site Number 616004

Torun, 87-100, Poland

Location

Investigational Site Number 642005

Alba Iulia, 510077, Romania

Location

Investigational Site Number 642006

Baia Mare, 430031, Romania

Location

Investigational Site Number 642009

Bucharest, 010976, Romania

Location

Investigational Site Number 642008

Bucharest, 022328, Romania

Location

Investigational Site Number 642001

Cluj-Napoca, 400015, Romania

Location

Investigational Site Number 642003

Cluj-Napoca, 400015, Romania

Location

Investigational Site Number 642004

Cluj-Napoca, 400015, Romania

Location

Investigational Site Number 642002

Cluj-Napoca, 400058, Romania

Location

Investigational Site Number 642012

Focşani, 620034, Romania

Location

Investigational Site Number 642007

Hunedoara, 331057, Romania

Location

Investigational Site Number 642013

Onești, 601048, Romania

Location

Investigational Site Number 643007

Moscow, 105425, Russia

Location

Investigational Site Number 643005

Moscow, 115478, Russia

Location

Investigational Site Number 643004

Moscow, 117997, Russia

Location

Investigational Site Number 643006

Moscow, 125284, Russia

Location

Investigational Site Number 643008

Obninsk, 249036, Russia

Location

Investigational Site Number 643001

Saint Petersburg, 197022, Russia

Location

Investigational Site Number 643010

Saint Petersburg, 197758, Russia

Location

Investigational Site Number 643003

Tula, 300053, Russia

Location

Investigational Site Number 643009

Yekaterinburg, 620036, Russia

Location

Investigational Site Number 710003

Cape Town, 7570, South Africa

Location

Investigational Site Number 710002

Durban, 4001, South Africa

Location

Investigational Site Number 710005

Johannesburg, 2193, South Africa

Location

Investigational Site Number 710004

Johannesburg, 2196, South Africa

Location

Investigational Site Number 710001

Pretoria, 0001, South Africa

Location

Investigational Site Number 410003

Seongnam, 463-707, South Korea

Location

Investigational Site Number 410002

Seoul, 110-744, South Korea

Location

Investigational Site Number 410004

Seoul, 120-752, South Korea

Location

Investigational Site Number 410005

Seoul, 135-710, South Korea

Location

Investigational Site Number 410001

Seoul, 138-736, South Korea

Location

Investigational Site Number 724003

Badalona, 08916, Spain

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Investigational Site Number 724002

Madrid, 28033, Spain

Location

Investigational Site Number 724008

Madrid, 28050, Spain

Location

Investigational Site Number 724006

Málaga, 29010, Spain

Location

Investigational Site Number 724005

Palma de Mallorca, 07010, Spain

Location

Investigational Site Number 724004

Sabadell, 08208, Spain

Location

Investigational Site Number 724007

Seville, 41071, Spain

Location

Investigational Site Number 158002

Taiching, 40447, Taiwan

Location

Investigational Site Number 158003

Tainan, 704, Taiwan

Location

Investigational Site Number 158001

Taipei, 100, Taiwan

Location

Investigational Site Number 788004

Sfax, 3029, Tunisia

Location

Investigational Site Number 788003

Sousse, 4000, Tunisia

Location

Investigational Site Number 788002

Tunis, 1006, Tunisia

Location

Investigational Site Number 792003

Antalya, 07059, Turkey (Türkiye)

Location

Investigational Site Number 792001

Bornova, 35100, Turkey (Türkiye)

Location

Investigational Site Number 792002

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number 826002

Birmingham, B18 7QH, United Kingdom

Location

Investigational Site Number 826004

Colchester, CO3 3NB, United Kingdom

Location

Investigational Site Number 826005

Glasgow, G11 6NT, United Kingdom

Location

Investigational Site Number 826006

Guildford, GU2 7XX, United Kingdom

Location

Investigational Site Number 826007

Manchester, M20 4BX, United Kingdom

Location

Investigational Site Number 826003

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Investigational Site Number 826001

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 35677318 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

• 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.

  PMID: 28809610 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; Prednisone; Prednisolone

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)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

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: April 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: April 17, 2017
• Results First Posted: October 11, 2016

Record last verified: 2016-08

Locations

US (21); RU (9); GB (7); AR (4); AU (15); PL (5); TW (3); BE (14); NL (5); ZA (5); CA (4); ES (8); BR (12); HU (5); CL (4); KR (5); TU (3); FR (11); PE (7); RO (11); DE (11)