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

Study Overview
=================
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.

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.

Conditions
-----------------
Metastatic Prostate Cancer

Intervention / Treatment
-----------------
* Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d
* Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d | Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d<br>* Docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d in 21 day cycles.<br>* Other names: Arm A;|
| Active Comparator: Arm B<br>docetaxel 75 mg/m2 + prednisone 10 mg/d | Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d<br>* Docetaxel 75 mg/m2 plus prednisone 10 mg/d in 21 day cycles.<br>* Other names: Arm B;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year radiologic progression free survival | Time from randomization to radiologic disease progression | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from randomization to death | Up to 3 years | 
| Radiologic progression free survival | Time from randomization to radiologic progression free survival | Up to 1 year | 
| PSA progression free survival | Time from randomization to PSA progression | Up to 3 weeks | 
| PSA response rate | 50% & 90% PSA reduction from randomisation | Up to 3 weeks | 
| Objective response rate | Response according RECIST criteria | Up to 12 weeks | 
| Quality of life rate | Quality of life according to FACT-P questionaire | Up to 12 weeks | 
| Time to skeletal-related event | Time from randomization to skeletal-related events | Up to 12 weeks | 
| Time to opiate use for cancer pain | Time from randomization to opiate use for cancer pain | Up to 3 weeks | 
| 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 | 
| Safety profile | Related adverse events per patient | Up to 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Abiraterone acetate, Metastatic prostate cancer