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

Metastatic Prostate Cancer Clinical Trial

— ABIDO  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02036060
• Other study ID #: ABIDO-SOGUG
• Secondary ID: 2013-003811-23
• Status: Completed
• Phase: Phase 2
• Start date: February 7, 2014
• Est. completion date: October 2020

Study information

• Verified date: October 2020
• Source: Spanish Oncology Genito-Urinary Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: October 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease Progression
• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellón	Castellón de la Plana	Castellón
Spain	Complejo Hospitalario Regional Reina Sofía	Córdoba
Spain	Hospital Universitario de Guadalajara	Guadalajara
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Ramón Y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Virgen de La Victoria	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Islas Baleares
Spain	Complejo Hospitalario Regional Virgen Del Rocio	Sevilla
Spain	Fundación Instituto Valenciano de Oncología	Valencia
Spain	Complexo Hospitalario Universitario de Vigo	Vigo	Pontevedra
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Spanish Oncology Genito-Urinary Group	Apices Soluciones S.L., Janssen, LP

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1 year radiologic progression free survival	Time from randomization to radiologic disease progression	1 year
Secondary	Overall survival	Time from randomization to death	Up to 3 years
Secondary	Radiologic progression free survival	Time from randomization to radiologic progression free survival	Up to 1 year
Secondary	PSA progression free survival	Time from randomization to PSA progression	Up to 3 weeks
Secondary	PSA response rate	50% & 90% PSA reduction from randomisation	Up to 3 weeks
Secondary	Objective response rate	Response according RECIST criteria	Up to 12 weeks
Secondary	Quality of life rate	Quality of life according to FACT-P questionaire	Up to 12 weeks
Secondary	Time to skeletal-related event	Time from randomization to skeletal-related events	Up to 12 weeks
Secondary	Time to opiate use for cancer pain	Time from randomization to opiate use for cancer pain	Up to 3 weeks
Secondary	Time to pain progression	Time from randomization to pain progression defined as an increase in median BPI score = 30% from baseline	Up to 3 weeks
Secondary	Safety profile	Related adverse events per patient	Up to 3 weeks