Abiraterone Acetate in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer.

Summary

Prostate cancer is the most frequently diagnosed non-skin cancer, and the second leading cause of men cancer death in the United States. Hormonal therapy remains a first-line treatment for metastatic prostate cancer. Initial responses to hormonal therapy with chemical or surgical castration are quite favorable, however, most patients will progress to a castration-resistant phase of the disease. Docetaxel is the primary chemotherapeutic option for patients with mCRPC.

Abiraterone is a novel, selective, irreversible, and potent inhibitor of 17-\[alpha\]-hydroxylase/17,20-lyase (CYP17) enzymatic activity that has recently been demonstrated to further reduce testosterone levels in the blood to undetectable range (\< 1 ng/dL) and is suggested to reduce de novo intratumor androgen synthesis. Abiraterone demonstrated activity in castration resistant prostate cancer patients previously treated with docetaxel chemotherapy. Recently, results of a phase III trial comparing abiraterone plus prednisone vs placebo plus prednisone in asymptomatic and without visceral metastasis, castration-resistant metastatic prostate cancer patients, demonstrated a better radiological progression free survival for abiraterone treated patients and a trend towards a better survival was clear for abiraterone treated patients.

No clinical evidence exists about efficacy of chemotherapy and antiandrogen therapy combination. All trials have been performed in patients in which LHRH agonist treatment was continued although there is not clear evidence about efficacy of hormonal treatment. Some retrospective studies suggest that androgen deprivation treatment should be maintained in chemotherapy treated patients. Abiraterone has been proved to suppress androgen levels to negative values, and to add efficacy to castration hormonal therapy. Combination of abiraterone with docetaxel chemotherapy seems promising adding efficacy to only docetaxel chemotherapy. A randomized phase II study comparing docetaxel + prednisone + abiraterone to docetaxel + prednisone in mCRPC in patients treated previously with abiraterone, seems promising to explore addition of efficacy to taxotere after abiraterone hormonal treatment.

Conditions

• Metastatic Prostate Cancer

Interventions

DRUG

docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d

Docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d in 21 day cycles.

DRUG

docetaxel 75 mg/m2 + prednisone 10 mg/d

Docetaxel 75 mg/m2 plus prednisone 10 mg/d in 21 day cycles.

Sponsors & Collaborators

• Janssen, LP

  collaborator INDUSTRY

• Apices Soluciones S.L.

  collaborator INDUSTRY

• Spanish Oncology Genito-Urinary Group

  lead OTHER

Principal Investigators

• Miguel A Climent, MD · Fundación Instituto Valenciano de Oncología

• José A Arranz, MD · HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN, Servicio de Oncología Médica

• Daniel E Castellano, MD · HOSPITAL UNIVERSITARIO 12 DE OCTUBRE,Servicio de Oncología Médica

• Begoña Mellado, MD · HOSPITAL CLINIC I PROVINCIAL DE BARCELONA, Servicio de Oncología Médica

• Albert Font, MD · HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL, Servicio de Oncología Médica

• Alfredo Sánchez, MD · CONSORCIO HOSPITALARIO PROVINCIAL DE CASTELLÓN, Servicio de Oncología Médica

• Emilio Esteban, MD · HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS, Servicio de Oncología Médica

• María I Sáez, MD · HOSPITAL VIRGEN DE LA VICTORIA, Servicio de Oncología Médica

• Carmen Santander, MD · HOSPITAL UNIVERSITARIO MIGUEL SERVET, Servicio de Oncología Médica

• Pablo Maroto, MD · HOSPITAL DE LA SANTA CREU I SANT PAU, Servicio de Oncología Médica

• Carmen Garcias de España, MD · HOSPITAL UNIVERSITARI SON ESPASES, Servicio de Oncología Médica

• Teresa Alonso, MD · HOSPITAL RAMÓN Y CAJAL, Servicio de Oncología Médica

• Javier Puente, MD · HOSPITAL CLÍNICO SAN CARLOS, Servicio de Oncología Médica

• Martín Lázaro, Md · COMPLEXO HOSPITALARIO UNIVERSITARIO DE VIGO, Servicio de Oncología Médica

• Javier Cassinello, MD · HOSPITAL UNIVERSITARIO DE GUADALAJARA, Servicio de Oncología Médica

• María J Méndez, MD · COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA, Servicio de Oncología Médica

• Begoña Perez-Valderrama, MD · COMPLEJO HOSPITALARIO REGIONAL VIRGEN DEL ROCIO, Servicio de Oncología Médica

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-02-07

Primary Completion

2020-06-30

Completion

2020-10-31

Countries

• Spain

Study Locations