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

Prostate Cancer Clinical Trial

— FIRSTANA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01308567
• Other study ID #: EFC11784
• Secondary ID: 2010-022064-12U1
• Status: Completed
• Phase: Phase 3
• Start date: May 5, 2011
• Est. completion date: May 2018

Study information

• Verified date: May 2019
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1168
• Est. completion date: May 2018
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Cabazitaxel (XRP6258)
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
• Docetaxel (XRP6976)
Pharmaceutical form: Solution for injection'; Route of administration: Intravenous
• Prednisone
Pharmaceutical form: Tablet; Route of administration: Oral

Locations

Country	Name	City	State
Australia	Investigational Site Number 036016	Bankstown
Australia	Investigational Site Number 036008	Camperdown
Australia	Investigational Site Number 036015	Coffs Harbour
Australia	Investigational Site Number 036001	Concord
Australia	Investigational Site Number 036017	Fitzroy
Australia	Investigational Site Number 036003	Herston
Australia	Investigational Site Number 036010	Hornsby
Australia	Investigational Site Number 036012	Kurralta Park
Australia	Investigational Site Number 036002	Parkville
Australia	Investigational Site Number 036009	South Brisbane
Australia	Investigational Site Number 036011	Subiaco
Australia	Investigational Site Number 036013	Wodonga
Belarus	Investigational Site Number 112001	Minsk
Belarus	Investigational Site Number 112002	Minsk
Belarus	Investigational Site Number 112004	Vitebsk
Brazil	Investigational Site Number 076006	Passo Fundo
Brazil	Investigational Site Number 076001	Porto Alegre
Brazil	Investigational Site Number 076002	Porto Alegre
Brazil	Investigational Site Number 076004	Rio De Janeiro
Brazil	Investigational Site Number 076009	Sao Jose Do Rio Preto
Brazil	Investigational Site Number 076005	Sao Paulo
Brazil	Investigational Site Number 076003	Uberlandia
Canada	Investigational Site Number 124002	London
Canada	Investigational Site Number 124007	Mississauga
Canada	Investigational Site Number 124005	Moncton
Canada	Investigational Site Number 124003	Montreal
Canada	Investigational Site Number 124004	Quebec
Canada	Investigational Site Number 124006	Toronto
China	Investigational Site Number 156005	Beijing
China	Investigational Site Number 156002	Shanghai
China	Investigational Site Number 156003	Shanghai
China	Investigational Site Number 156004	Shanghai
Czechia	Investigational Site Number 203002	Brno
Czechia	Investigational Site Number 203003	Novy Jicin
Czechia	Investigational Site Number 203001	Olomouc
Czechia	Investigational Site Number 203004	Praha 2
Denmark	Investigational Site Number 208004	Ålborg
Denmark	Investigational Site Number 208002	Herlev
Denmark	Investigational Site Number 208001	København Ø
Denmark	Investigational Site Number 208003	Odense C
Finland	Investigational Site Number 246002	Helsinki
Finland	Investigational Site Number 246001	Kuopio
Finland	Investigational Site Number 246003	Turku
France	Investigational Site Number 250010	Besancon Cedex
France	Investigational Site Number 250002	Bordeaux Cedex
France	Investigational Site Number 250006	Caen Cedex 05
France	Investigational Site Number 250005	Lyon
France	Investigational Site Number 250003	Paris Cedex 05
France	Investigational Site Number 250004	Paris Cedex 10
France	Investigational Site Number 250001	Paris Cedex 15
France	Investigational Site Number 250007	Poitiers Cedex
France	Investigational Site Number 250008	Suresnes
France	Investigational Site Number 250009	Villejuif
Germany	Investigational Site Number 276003	Aachen
Germany	Investigational Site Number 276005	Berlin
Germany	Investigational Site Number 276001	Düsseldorf
Germany	Investigational Site Number 276004	Erlangen
Germany	Investigational Site Number 276002	Homburg
Germany	Investigational Site Number 276006	München
Israel	Investigational Site Number 376004	Kfar Saba
Israel	Investigational Site Number 376003	Petah-Tikva
Israel	Investigational Site Number 376002	Tel Aviv
Italy	Investigational Site Number 380001	Arezzo
Italy	Investigational Site Number 380004	Bari
Italy	Investigational Site Number 380003	Orbassano
Italy	Investigational Site Number 380005	Roma
Italy	Investigational Site Number 380002	Trento
Japan	Investigational Site Number 392001	Bunkyo-Ku
Japan	Investigational Site Number 392003	Chiba-Shi
Japan	Investigational Site Number 392006	Kashiwa-Shi
Japan	Investigational Site Number 392005	Koto-Ku
Japan	Investigational Site Number 392002	Osaka Sayama-Shi
Japan	Investigational Site Number 392004	Osaka-Shi
Mexico	Investigational Site Number 484007	Acapulco
Mexico	Investigational Site Number 484008	Aguascalientes
Mexico	Investigational Site Number 484003	D.f.
Mexico	Investigational Site Number 484004	Guadalajara
Mexico	Investigational Site Number 484009	Merida
Mexico	Investigational Site Number 484005	Queretaro
Mexico	Investigational Site Number 484002	San Luis Potosi
Mexico	Investigational Site Number 484006	Zapopan
Peru	Investigational Site Number 604001	Lima
Peru	Investigational Site Number 604002	Lima
Peru	Investigational Site Number 604005	Lima
Peru	Investigational Site Number 604006	Lima
Poland	Investigational Site Number 616002	Bydgoszcz
Poland	Investigational Site Number 616001	Gdansk
Poland	Investigational Site Number 616003	Koscierzyna
Poland	Investigational Site Number 616005	Lodz
Poland	Investigational Site Number 616004	Poznan
Portugal	Investigational Site Number 620003	Coimbra
Portugal	Investigational Site Number 620004	Lisboa
Portugal	Investigational Site Number 620005	Lisboa
Portugal	Investigational Site Number 620001	Porto
Portugal	Investigational Site Number 620002	Porto
Romania	Investigational Site Number 642004	Baia Mare
Romania	Investigational Site Number 642008	Bucharest
Romania	Investigational Site Number 642005	Bucuresti
Romania	Investigational Site Number 642002	Cluj Napoca
Romania	Investigational Site Number 642003	Cluj Napoca
Romania	Investigational Site Number 642007	Hunedoara
Russian Federation	Investigational Site Number 643004	Ekaterinburg
Russian Federation	Investigational Site Number 643008	Moscow
Russian Federation	Investigational Site Number 643003	Omsk
Russian Federation	Investigational Site Number 643002	Pyatigorsk
Russian Federation	Investigational Site Number 643007	Ryazan
Russian Federation	Investigational Site Number 643005	St-Petersburg
Russian Federation	Investigational Site Number 643001	Tomsk
Russian Federation	Investigational Site Number 643006	Yaroslavl
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724002	Barcelona
Spain	Investigational Site Number 724007	Barcelona
Spain	Investigational Site Number 724003	Hospitalet De Llobregat
Spain	Investigational Site Number 724004	Madrid
Spain	Investigational Site Number 724005	Madrid
Spain	Investigational Site Number 724006	Santiago De Compostela
Sweden	Investigational Site Number 752003	Malmö
Sweden	Investigational Site Number 752002	Stockholm
Sweden	Investigational Site Number 752001	Uppsala
Taiwan	Investigational Site Number 158004	Kaohsiung
Taiwan	Investigational Site Number 158002	Taichung
Taiwan	Investigational Site Number 158001	Taipei
Taiwan	Investigational Site Number 158003	Tao-Yuan
Turkey	Investigational Site Number 792002	Ankara
Turkey	Investigational Site Number 792001	Istanbul
Ukraine	Investigational Site Number 804009	Cherkasy
Ukraine	Investigational Site Number 804004	Dnipropetrovsk
Ukraine	Investigational Site Number 804010	Donetsk
Ukraine	Investigational Site Number 804006	Ivano-Frankivsk
Ukraine	Investigational Site Number 804003	Kharkov
Ukraine	Investigational Site Number 804001	Kyiv
Ukraine	Investigational Site Number 804002	Kyiv
Ukraine	Investigational Site Number 804007	Lutsk
Ukraine	Investigational Site Number 804005	Uzhgorod
Ukraine	Investigational Site Number 804008	Zaporizhzhya
United States	Investigational Site Number 840026	Akron	Ohio
United States	Investigational Site Number 840033	Albuquerque	New Mexico
United States	Investigational Site Number 840009	Anaheim	California
United States	Investigational Site Number 840014	Bakersfield	California
United States	Investigational Site Number 840013	Boca Raton	Florida
United States	Investigational Site Number 840138	Boston	Massachusetts
United States	Investigational Site Number 840238	Boston	Massachusetts
United States	Investigational Site Number 840038	Brookline	Massachusetts
United States	Investigational Site Number 840028	Chattanooga	Tennessee
United States	Investigational Site Number 840023	Cleveland	Ohio
United States	Investigational Site Number 840015	Decatur	Illinois
United States	Investigational Site Number 840019	Denver	Colorado
United States	Investigational Site Number 840005	Detroit	Michigan
United States	Investigational Site Number 840032	Dunmore	Pennsylvania
United States	Investigational Site Number 840017	East Orange	New Jersey
United States	Investigational Site Number 840035	Jacksonville	Florida
United States	Investigational Site Number 840016	Kansas City	Missouri
United States	Investigational Site Number 840020	Lincoln	Nebraska
United States	Investigational Site Number 840004	Muscle Shoals	Alabama
United States	Investigational Site Number 840037	Myrtle Beach	South Carolina
United States	Investigational Site Number 840008	New Orleans	Louisiana
United States	Investigational Site Number 840010	Paducah	Kentucky
United States	Investigational Site Number 840007	Pawtucket	Rhode Island
United States	Investigational Site Number 840001	Port Saint Lucie	Florida
United States	Investigational Site Number 840036	Raleigh	North Carolina
United States	Investigational Site Number 840006	Rockville	Maryland
United States	Investigational Site Number 840030	Sacramento	California
United States	Investigational Site Number 840021	Saint Louis Park	Minnesota
United States	Investigational Site Number 840003	San Bernardino	California
United States	Investigational Site Number 840012	San Francisco	California
United States	Investigational Site Number 840011	Washington	North Carolina
United States	Investigational Site Number 840018	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belarus,  Brazil,  Canada,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Japan,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival (PFS)	PFS: time interval between date of randomization to date of first occurrence of any of following events: tumor progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; Prostate Specific Antigen (PSA) progression; pain progression or death due to any cause. Analysis was performed by Kaplan-Meier method.	Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)
Secondary	Time to Tumor Progression Free Survival	Time to tumor progression free survival was defined as the time interval between randomization and the date of first occurrence of tumor progression (assessed using RECIST version 1.1) or death, whichever was earlier. Analysis was performed by Kaplan-Meier method.	Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Secondary	Percentage of Participants With Overall Objective Tumor Response	Overall objective tumor response was defined as having a partial response (PR) or complete response (CR) according to the RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Secondary	Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS)	Time to PSA-PFS: time interval between date of randomization & first occurrence of PSA progression/ death, whichever was earlier. PSA progression:1) In PSA responders(=50% decline from baseline PSA of =10 ng/mL):increase of =25%(at least 2 ng/mL)over nadir value, confirmed by second PSA value at least 3 weeks later;2)In PSA non-responders(not achieved =50% decline from baseline PSA =10 ng/mL):increase of =25% (at least 2 ng/mL) over baseline value, confirmed by second PSA value at least 3 weeks later;3)In participants not eligible for PSA response(baseline PSA <10 ng/mL):(a)in participants with baseline PSA>0 ng/mL&<10 ng/mL: increase in PSA by 25% (at least 2 ng/mL) above baseline level, confirmed by second PSA value at least 3weeks apart;(b)in participants with baseline value=0ng/mL: a post baseline PSA value =2ng/mL.Early rise in PSA only indicated progression if it was associated with another sign of DP or if it continued beyond 12 weeks. Analysis performed by Kaplan-Meier method.	Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Secondary	Percentage of Participants With PSA Response	PSA response was defined as =50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in participants with baseline PSA value =10 ng/mL.	Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
Secondary	Time to Pain Progression Free Survival (Pain PFS)	Time to pain PFS was defined as the time interval between date of randomization and the date of the first occurrence of pain progression or death, whichever was earlier. Pain progression was defined as an increase of =1 point in the median present pain intensity (PPI) score from the nadir confirmed by a second assessment at least 3 weeks later or =25 % increase in the mean analgesic score from baseline, due to cancer related pain confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was performed by Kaplan-Meier method.	Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)
Secondary	Percentage of Participants With Pain Response	Pain response was defined as either a =2-point decrease from baseline median PPI score without increase in analgesic score, or a =50% decrease in analgesic use from baseline mean analgesic score (only in participants with baseline mean analgesic score=10) without increase in the pain. Either criterion was maintained for 2 consecutive evaluations at least 3 weeks apart. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points.	Baseline until pain progression, death or study cut-off date (maximum duration: 51 months)
Secondary	Skeletal Related Events (SRE) Free Survival	SRE free survival was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SRE or death due to any cause, whichever was earlier. SRE were assessed by clinical evaluation. Occurrence of SRE was defined as: pathological fracture(s) and/or spinal cord compression; need for bone irradiation, including radioisotopes or bone surgery; and change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the setting of increased pain) to treat bone pain. Analysis was performed by Kaplan-Meier method.	Baseline until occurrence of first SRE or death (maximum duration: 51 months)
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL)	FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to156 with higher score indicated better quality of life with fewer symptoms.	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)
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL	FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). Physical well being, functional well being, and prostate-specific concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms.	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)