Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsSexo: MALE

Criterios de inclusión

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).

Criterios de exclusión

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.

Intervenciones

drug

Cabazitaxel (XRP6258)

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

drug

Prednisone (or Prednisolone)

Pharmaceutical form: Tablet Route of administration: Oral

Ubicaciones

Investigational Site Number 032002

Buenos Aires, Argentina

Investigational Site Number 032001

Rosario, Argentina

Investigational Site Number 032003

Salta, Argentina

Investigational Site Number 032004

Santa Fe, Argentina

Patrocinadores

PrincipalSanofi

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