Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

Study Overview
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Brief Summary
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This is a randomized phase 3 trial aiming to compare the efficacy of docetaxel and hormone therapy as second line treatment in patients with mCRPC progressing after therapy with abiraterone or enzalutamide.

Detailed Description
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Patients will be randomized 1:1 to receive docetaxel or hormone therapy (abiraterone or enzalutamide based on previous treatment). Docetaxel (standard) will be administered for 10 cycles (maximum). Hormone therapy (experimental) will be administered until progression or unacceptable toxicity.

Official Title
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A Randomized Multicenter Phase III Trial Comparing Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

Conditions
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Metastatic Castration-resistent Prostate Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Abiraterone Acetate or Enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate Distant metastatic disease Previous first line treatment with abiraterone or enzalutamide for 6 cycles interrupted at least 2 weeks before randomization Patients must be ≥ 18 years of age Patients must have castrate serum level of testosterone of < 0.5 ng/mL ( 1.7 nmol/L) Asymptomatic or Oligosymptomatic disease Progressive disease according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria ECOG performance status (PS) of 0-2 Sexually active males must use an accepted and effective method birth control measure Written informed consent Exclusion Criteria: Prior exposure to docetaxel or abiraterone for treatment of hormone-sensitive metastatic prostate cancer (mHSPC) History of adrenal insufficiency or hypoaldosteronism Any medical condition that would make prednisone use contraindicated Any medical condition that would make docetaxel use contraindicated Patients unable to swallow orally administered medication Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) requiring antiretroviral therapy Other malignancy within the last 5 years, except for adequately treated non melanoma skin cancer, bladder cancer (pTis, pTa, pT1) or other solid tumours curatively treated with no evidence of disease for > 5 years Participation in another clinical study with an investigational product within 30 days prior to randomization Persistent toxicities [>Common Terminology Criteria for Adverse Event (CTCAE) grade 1)] caused by previous cancer therapy prior to randomization Uncontrolled medical conditions including diabetes mellitus. Clinically significant cardiovascular disease (e.g.: uncontrolled hypertension or arrhythmia, unstable angina pectoris, congestive heart failure (CHF), vascular disease (arterial thrombosis) and myocardial infarction within < 6 months Left ventricular ejection fraction < 50% Peripheral neuropathy [> CTCAE grade 2] Inadequate bone marrow function defined as: haemoglobin < 9.0 g/dL absolute neutrophils count (ANC) <1.5 x 109/L (> 1500 per mm3) platelet count <100 x 109/L (>100,000 per mm3) Inadequate renal and hepatic function, defined as: total serum bilirubin > 1,0 x ULN AST/SGOT o ALT/SGPT > 1,5 x ULN calculated creatinine clearance < 40 mL/min potassium level < 3,5 mmol/L Child-Pugh class C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment Comparative Randomized Phase 3 Design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Docetaxel<br>Docetaxel 75 mg/m2 intravenous (iv) infusion every 3 weeks plus oral prednisone 5 mg twice daily for a maximum of 10 cycles. | Drug: Docetaxel<br>* Docetaxel 75 mg/m2 intravenous (iv) infusion every 3 weeks plus oral prednisone 5 mg twice daily for a maximum of 10 cycles.<br>|
| Experimental: Abiraterone or Enzalutamide<br>Patient will receive Abiraterone or Enzalutamide based on previous treatment. Abiraterone given orally at the dose of 1000 mg daily plus oral prednisone 5 mg twice daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment. Enzalutamide given orally at the dose of 160 mg daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment. | Drug: Abiraterone Acetate or Enzalutamide<br>* Patient will receive Abiraterone or Enzalutamide based on previous treatment. Abiraterone given orally at the dose of 1000 mg daily plus oral prednisone 5 mg twice daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment. Enzalutamide given orally at the dose of 160 mg daily until progression or unacceptable toxicity. One course of therapy corresponds to four weeks of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from randomization until death | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS is defined as the time elapsed from the date of randomization to the date of progression, as defined by investigators, or the date of death, whichever comes first. | up to 5 years | 
| Time to Prostate-Specific Antigen (PSA) Progression | as determined by investigator | up to 5 years | 
| Incidence of symptomatic skeletal events (SSE) | reporting the incidence and types of skeletal related events | up to 5 years | 
| Time to symptomatic skeletal event (SSE) | Time from the date of randomization to the date of documented symptomatic skeletal event | up to 5 years | 
| Time to Pain Progression | Time from the date of randomization to the date of pain progression | up to 5 years | 
| Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 | graded according to Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 | baseline, during treatment (every 4 weeks) up to 5 years | 
| Determination of changes in quality of life | EORTC QLQ-C30, a quality of life questionnaires, composed by 30 items graded from1 (not at all) to 4 (very much) after 1 year from the diagnosis | baseline, during treatment up to 5 years | 
| Radiographic response (bone lesions) | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | up to 5 years | 
| Radiographic response (soft tissue lesions) | Prostate Cancer Working Group 3 (PCWG3) criteria | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic castration-resistent prostate cancer, asymptomatic or oligosymptomatic, hormone therapy, docetaxel