Clinical trial NCT02036060: Abiraterone Acetate in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer.
Official title: Abiraterone Acetate Maintenance in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer. Randomized Phase II Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Keywords: Metastatic prostate cancer
Abiraterone acetate
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
Collaborators: name: Janssen, LP
name: Apices Soluciones S.L.
First posted: 2014-01-14
Enrollment: 119
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: 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.


Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent
* Male aged 18 years and above
* Histologically or cytologically confirmed adenocarcinoma of the prostate.
* Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI.
* Prostate cancer progression to previous castration treatment documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria or bone scan progression
* Asymptomatic or mildly symptomatic from prostate cancer
* Surgically or medically castrated, with testosterone levels of \< 50 ng/dL (\< 2.0 nM).
* Previous anti-androgen therapy and progression after withdrawal.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Hemoglobin \>= 10.0 g/dL independent of transfusion
* Platelet count \>= 100,000/µL
* Serum albumin \>= 3.5 g/dL
* Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance \>= 60 mL/min
* Serum potassium \>= 3.5 mmol/L
* Liver function: a. Serum bilirubin \< 1.5 x ULN (except for patients with documented Gilbert's disease) b. AST or ALT \< 2.5 x ULN
* Life expectancy of at least 6 months
* Patients who have partners of childbearing potential must be willing to use a method of birth control

Exclusion Criteria:

* Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
* Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily.
* Pathological finding consistent with small cell carcinoma of the prostate
* Liver or visceral organ metastasis
* Known brain metastasis
* Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1
* Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
* Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day
* Radiation or radionuclide therapy for treatment of metastatic CRPC
* Previously treated with ketoconazole for prostate cancer for greater than 7 days
* Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
* Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1
* Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1
* Uncontrolled hypertension (systolic BP \>= 160 mmHg or diastolic BP \>= 95 mmHg).
* Active or symptomatic viral hepatitis or chronic liver disease
* History of pituitary or adrenal dysfunction
* Clinically significant heart disease
* Atrial Fibrillation, or other cardiac arrhythmia requiring therapy
* Other malignancy, except non-melanoma skin cancer, with a \>= 30% probability of recurrence within 24 months
* Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
* Any condition which, in the opinion of the investigator, would preclude participation in this trial.

Primary outcomes:
measure: 1 year radiologic progression free survival
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 3 years
measure: Radiologic progression free survival
timeFrame: Up to 1 year
measure: PSA progression free survival
timeFrame: Up to 3 weeks
measure: PSA response rate
timeFrame: Up to 3 weeks
measure: Objective response rate
timeFrame: Up to 12 weeks
measure: Quality of life rate
timeFrame: Up to 12 weeks
measure: Time to skeletal-related event
timeFrame: Up to 12 weeks
measure: Time to opiate use for cancer pain
timeFrame: Up to 3 weeks
measure: Time to pain progression
timeFrame: Up to 3 weeks
measure: Safety profile
timeFrame: Up to 3 weeks
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
state: Barcelona
city: Castellón de la Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
state: Castellón
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Islas Baleares
city: Vigo
country: Spain
facility: Complexo Hospitalario Universitario de Vigo
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Córdoba
country: Spain
facility: Complejo Hospitalario Regional Reina Sofía
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón Y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Virgen de La Victoria
city: Sevilla
country: Spain
facility: Complejo Hospitalario Regional Virgen Del Rocio
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Fundación Instituto Valenciano de Oncología
name: Miguel A Climent, MD
role: STUDY_CHAIR
affiliation: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN, Servicio de Oncología Médica
name: José A Arranz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARIO 12 DE OCTUBRE,Servicio de Oncología Médica
name: Daniel E Castellano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL CLINIC I PROVINCIAL DE BARCELONA, Servicio de Oncología Médica
name: Begoña Mellado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL, Servicio de Oncología Médica
name: Albert Font, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CONSORCIO HOSPITALARIO PROVINCIAL DE CASTELLÓN, Servicio de Oncología Médica
name: Alfredo Sánchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS, Servicio de Oncología Médica
name: Emilio Esteban, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL VIRGEN DE LA VICTORIA, Servicio de Oncología Médica
name: María I Sáez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARIO MIGUEL SERVET, Servicio de Oncología Médica
name: Carmen Santander, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL DE LA SANTA CREU I SANT PAU, Servicio de Oncología Médica
name: Pablo Maroto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARI SON ESPASES, Servicio de Oncología Médica
name: Carmen Garcias de España, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL RAMÓN Y CAJAL, Servicio de Oncología Médica
name: Teresa Alonso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL CLÍNICO SAN CARLOS, Servicio de Oncología Médica
name: Javier Puente, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEXO HOSPITALARIO UNIVERSITARIO DE VIGO, Servicio de Oncología Médica
name: Martín Lázaro, Md
role: PRINCIPAL_INVESTIGATOR
affiliation: HOSPITAL UNIVERSITARIO DE GUADALAJARA, Servicio de Oncología Médica
name: Javier Cassinello, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA, Servicio de Oncología Médica
name: María J Méndez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: COMPLEJO HOSPITALARIO REGIONAL VIRGEN DEL ROCIO, Servicio de Oncología Médica
name: Begoña Perez-Valderrama, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Climent MA, Font A, Duran I, Puente J, Jose Mendez-Vidal M, Saez MI, Santander Lobera C, Angel Arranz Arija J, Gonzalez-Del-Alba A, Sanchez-Hernandez A, Juan Fita MJ, Esteban E, Alonso-Gordoa T, Mellado Gonzalez B, Maroto P, Lazaro-Quintela M, Cassinello-Espinosa J, Perez-Valderrama B, Garcias C, Castellano D. A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. Eur J Cancer. 2022 Nov;175:110-119. doi: 10.1016/j.ejca.2022.08.002. Epub 2022 Sep 11.