Clinical trial NCT01308580: Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 1200
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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From baseline up to death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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)
measure: Time to Tumor Progression
timeFrame: From baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
measure: Percentage of Participants With Overall Objective Tumor Response
timeFrame: From baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
measure: Time to PSA Progression
timeFrame: From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
measure: Percentage of Participants With PSA Response
timeFrame: From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)
measure: Time to Pain Progression
timeFrame: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
measure: Percentage of Participants With Pain Response
timeFrame: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
measure: 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)
timeFrame: 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)
measure: Change From Baseline in FACT-P:Total Score as a Measure of HRQoL
timeFrame: 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)
measure: Percentage of Participants With FACT-P Total Score Response
timeFrame: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
measure: Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales
timeFrame: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
measure: Time to Definitive Deterioration of ECOG PS Score From Baseline
timeFrame: From baseline until death or study cut-off date (maximum duration: 48 months)
measure: Time to Definitive Weight Loss by 5% and 10% From Baseline
timeFrame: From baseline until death or study cut-off date (maximum duration: 48 months)
measure: Time to First Definitive Consumption of Narcotic Medication
timeFrame: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first administration of study treatment until 30 days after the last administration of study treatment (Maximum duration: 48 months)
measure: Plasma Clearance (CL) for Cabazitaxel
timeFrame: 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
measure: Plasma Steady State Volume of Distribution (Vss) for Cabazitaxel
timeFrame: 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
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Investigational Site Number 840002
state: Alabama
city: Hot Springs
country: United States
facility: Investigational Site Number 840004
state: Arkansas
city: Anaheim
country: United States
facility: Investigational Site Number 840008
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 840010
state: California
city: San Bernardino
country: United States
facility: Investigational Site Number 840001
state: California
city: Stamford
country: United States
facility: Investigational Site Number 840021
state: Connecticut
city: Jacksonville
country: United States
facility: Investigational Site Number 840023
state: Florida
city: Lakeland
country: United States
facility: Investigational Site Number 840013
state: Florida
city: Port St. Lucie
country: United States
facility: Investigational Site Number 840003
state: Florida
city: New Orleans
country: United States
facility: Investigational Site Number 840007
state: Louisiana
city: Baltimore
country: United States
facility: Investigational Site Number 840014
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840005
state: Maryland
city: St Louis Park
country: United States
facility: Investigational Site Number 840017
state: Minnesota
city: Jackson
country: United States
facility: Investigational Site Number 840011
state: Mississippi
city: Lincoln
country: United States
facility: Investigational Site Number 840016
state: Nebraska
city: East Orange
country: United States
facility: Investigational Site Number 840015
state: New Jersey
city: Raleigh
country: United States
facility: Investigational Site Number 840024
state: North Carolina
city: Akron
country: United States
facility: Investigational Site Number 840020
state: Ohio
city: Pawtucket
country: United States
facility: Investigational Site Number 840006
state: Rhode Island
city: Chattanooga
country: United States
facility: Investigational Site Number 840025
state: Tennessee
city: Corpus Christi
country: United States
facility: Investigational Site Number 840012
state: Texas
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032002
city: Rosario
country: Argentina
facility: Investigational Site Number 032001
city: Salta
country: Argentina
facility: Investigational Site Number 032003
city: Santa Fe
country: Argentina
facility: Investigational Site Number 032004
city: Adelaide
country: Australia
facility: Investigational Site Number 036014
city: Bankstown
country: Australia
facility: Investigational Site Number 036013
city: Box Hill
country: Australia
facility: Investigational Site Number 036010
city: Camperdown
country: Australia
facility: Investigational Site Number 036012
city: Coffs Harbour
country: Australia
facility: Investigational Site Number 036008
city: Concord
country: Australia
facility: Investigational Site Number 036001
city: Elizabeth Vale
country: Australia
facility: Investigational Site Number 036015
city: Fitzroy
country: Australia
facility: Investigational Site Number 036009
city: Garran
country: Australia
facility: Investigational Site Number 036007
city: Heidelberg West
country: Australia
facility: Investigational Site Number 036005
city: Malvern
country: Australia
facility: Investigational Site Number 036002
city: South Brisbane
country: Australia
facility: Investigational Site Number 036006
city: Subiaco
country: Australia
facility: Investigational Site Number 036016
city: Wahroonga
country: Australia
facility: Investigational Site Number 036003
city: Wodonga
country: Australia
facility: Investigational Site Number 036004
city: Antwerpen
country: Belgium
facility: Investigational Site Number 056007
city: Brussel
country: Belgium
facility: Investigational Site Number 056008
city: Bruxelles
country: Belgium
facility: Investigational Site Number 056001
city: Bruxelles
country: Belgium
facility: Investigational Site Number 056002
city: Charleroi
country: Belgium
facility: Investigational Site Number 056009
city: Gent
country: Belgium
facility: Investigational Site Number 056003
city: Godinne
country: Belgium
facility: Investigational Site Number 056012
city: Haine-Saint-Paul
country: Belgium
facility: Investigational Site Number 056016
city: Hasselt
country: Belgium
facility: Investigational Site Number 056005
city: Libramont
country: Belgium
facility: Investigational Site Number 056010
city: Liège
country: Belgium
facility: Investigational Site Number 056013
city: Ottignies
country: Belgium
facility: Investigational Site Number 056011
city: Roeselare
country: Belgium
facility: Investigational Site Number 056004
city: Turnhout
country: Belgium
facility: Investigational Site Number 056006
city: Fortaleza
country: Brazil
facility: Investigational Site Number 076016
city: Ijui
country: Brazil
facility: Investigational Site Number 076012
city: Mogi Das Cruzes
country: Brazil
facility: Investigational Site Number 076015
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076014
city: Rio De Janeiro
country: Brazil
facility: Investigational Site Number 076010
city: Salvador
country: Brazil
facility: Investigational Site Number 076007
city: Sao Jose Do Rio Preto
country: Brazil
facility: Investigational Site Number 076003
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076009
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076001
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076013
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076008
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076002
city: Greenfield Park
country: Canada
facility: Investigational Site Number 124002
city: Oshawa
country: Canada
facility: Investigational Site Number 124001
city: Ottawa
country: Canada
facility: Investigational Site Number 124003
city: Owen Sound
country: Canada
facility: Investigational Site Number 124005
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Santiago
country: Chile
facility: Investigational Site Number 152004
city: Santiago
country: Chile
facility: Investigational Site Number 152002
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 152001
city: Avignon Cedex 9
country: France
facility: Investigational Site Number 250005
city: Hyeres
country: France
facility: Investigational Site Number 250008
city: La Roche Sur Yon
country: France
facility: Investigational Site Number 250001
city: Nantes Cedex 2
country: France
facility: Investigational Site Number 250002
city: Nimes
country: France
facility: Investigational Site Number 250004
city: Paris
country: France
facility: Investigational Site Number 250010
city: Reims Cedex
country: France
facility: Investigational Site Number 250009
city: Reims
country: France
facility: Investigational Site Number 250007
city: Saint Brieuc Cedex
country: France
facility: Investigational Site Number 250006
city: Toulouse Cedex 03
country: France
facility: Investigational Site Number 250011
city: Toulouse Cedex 09
country: France
facility: Investigational Site Number 250003
city: Aachen
country: Germany
facility: Investigational Site Number 276003
city: Dresden
country: Germany
facility: Investigational Site Number 276007
city: Düsseldorf
country: Germany
facility: Investigational Site Number 276004
city: Erlangen
country: Germany
facility: Investigational Site Number 276001
city: Hamburg
country: Germany
facility: Investigational Site Number 276011
city: Hamburg
country: Germany
facility: Investigational Site Number 276005
city: Homburg
country: Germany
facility: Investigational Site Number 276010
city: München
country: Germany
facility: Investigational Site Number 276006
city: Nürtingen
country: Germany
facility: Investigational Site Number 276012
city: Tübingen
country: Germany
facility: Investigational Site Number 276008
city: Wuppertal
country: Germany
facility: Investigational Site Number 276002
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Budapest
country: Hungary
facility: Investigational Site Number 348005
city: Budapest
country: Hungary
facility: Investigational Site Number 348004
city: Miskolc
country: Hungary
facility: Investigational Site Number 348006
city: Pécs
country: Hungary
facility: Investigational Site Number 348003
city: Seongnam
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410005
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Arnhem
country: Netherlands
facility: Investigational Site Number 528005
city: Blaricum
country: Netherlands
facility: Investigational Site Number 528003
city: Hoofddorp
country: Netherlands
facility: Investigational Site Number 528004
city: Nijmegen
country: Netherlands
facility: Investigational Site Number 528002
city: Zwolle
country: Netherlands
facility: Investigational Site Number 528001
city: Arequipa
country: Peru
facility: Investigational Site Number 604003
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 604007
city: Lima
country: Peru
facility: Investigational Site Number 604002
city: Lima
country: Peru
facility: Investigational Site Number 604004
city: Lima
country: Peru
facility: Investigational Site Number 604005
city: Lubin
country: Poland
facility: Investigational Site Number 616006
city: Olsztyn
country: Poland
facility: Investigational Site Number 616002
city: Rybnik
country: Poland
facility: Investigational Site Number 616001
city: Siedlce
country: Poland
facility: Investigational Site Number 616005
city: Torun
country: Poland
facility: Investigational Site Number 616004
city: Alba Iulia
country: Romania
facility: Investigational Site Number 642005
city: Baia Mare
country: Romania
facility: Investigational Site Number 642006
city: Bucuresti
country: Romania
facility: Investigational Site Number 642009
city: Bucuresti
country: Romania
facility: Investigational Site Number 642008
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642001
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642003
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642004
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642002
city: Focsani
country: Romania
facility: Investigational Site Number 642012
city: Hunedoara
country: Romania
facility: Investigational Site Number 642007
city: Onesti
country: Romania
facility: Investigational Site Number 642013
city: Ekaterinburg
country: Russian Federation
facility: Investigational Site Number 643009
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643007
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643004
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643006
city: Obninsk
country: Russian Federation
facility: Investigational Site Number 643008
city: St.Petersburg
country: Russian Federation
facility: Investigational Site Number 643001
city: St.Petersburg
country: Russian Federation
facility: Investigational Site Number 643010
city: Tula
country: Russian Federation
facility: Investigational Site Number 643003
city: Cape Town
country: South Africa
facility: Investigational Site Number 710003
city: Durban
country: South Africa
facility: Investigational Site Number 710002
city: Johannesburg
country: South Africa
facility: Investigational Site Number 710005
city: Johannesburg
country: South Africa
facility: Investigational Site Number 710004
city: Pretoria
country: South Africa
facility: Investigational Site Number 710001
city: Badalona
country: Spain
facility: Investigational Site Number 724003
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Madrid
country: Spain
facility: Investigational Site Number 724002
city: Madrid
country: Spain
facility: Investigational Site Number 724008
city: Málaga
country: Spain
facility: Investigational Site Number 724006
city: Palma De Mallorca
country: Spain
facility: Investigational Site Number 724005
city: Sabadell
country: Spain
facility: Investigational Site Number 724004
city: Sevilla
country: Spain
facility: Investigational Site Number 724007
city: Taiching
country: Taiwan
facility: Investigational Site Number 158002
city: Tainan
country: Taiwan
facility: Investigational Site Number 158003
city: Taipei
country: Taiwan
facility: Investigational Site Number 158001
city: Sfax
country: Tunisia
facility: Investigational Site Number 788004
city: Sousse
country: Tunisia
facility: Investigational Site Number 788003
city: Tunis
country: Tunisia
facility: Investigational Site Number 788002
city: Antalya
country: Turkey
facility: Investigational Site Number 792003
city: Bornova
country: Turkey
facility: Investigational Site Number 792001
city: Istanbul
country: Turkey
facility: Investigational Site Number 792002
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 826002
city: Colchester
country: United Kingdom
facility: Investigational Site Number 826004
city: Glasgow
country: United Kingdom
facility: Investigational Site Number 826005
city: Guildford
country: United Kingdom
facility: Investigational Site Number 826006
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826007
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number 826003
city: Sutton
country: United Kingdom
facility: Investigational Site Number 826001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
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: 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.
citation: Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.