Patient Preference of Apalutamide Versus Enzalutamide in Patients With Recurrent or Metastatic Hormone-Sensitive Prostate Cancer

Study Overview
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Brief Summary
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This is a prospective, open-label, randomized, controlled, cross-over trial assessing patient preference for apalutamide versus enzalutamide in 146 male patients with recurrent or metastatic hormone-sensitive prostate cancer. The primary objective is to investigate whether there is any difference in patient preference between apalutamide and enzalutamide in patients with recurrent or metastatic hormone-sensitive prostate cancer.

Detailed Description
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This is a prospective, open-label, randomized, controlled, cross-over trial assessing patient preference for apalutamide versus enzalutamide in 146 male patients with recurrent or metastatic hormone-sensitive prostate cancer The primary outcome is patient preference, which serves as an indicator covering different aspects of treatment-related effects, and this would be most important in a patient's perspective. The quality of life, psychological and cognitive changes following apalutamide and enzalutamide in a comprehensive manner will be investigated. Patient will receive two 12-weeks treatment periods with a 5-week wash-out period between the treatment periods. Patients will receive Apalutamide and Enzulutamide sequentially. Patient, physician and caregiver preferences will be assessed at the end of the second treatment period. Other secondary outcomes on health-related quality of life measures, psychological assessment scores and cognitive assessment scores shall be assessed before and the end of first treatment and second treatment period.

Official Title
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Patient Preference of Apalutamide Versus Enzalutamide in Patients With Recurrent or Metastatic Hormone-Sensitive Prostate Cancer: An Open-label, Randomized, Cross-Over Trial.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Apalutamide
* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old or above with informed consent Histological diagnosis of adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Androgen deprivation therapy started at least 28 days prior to randomization Patients should be having one of the following diseases and treatment conditions: Recurrent prostate cancer following radical prostatectomy or radiotherapy, which do not fall into high-risk or high-volume categories Metastatic hormone-sensitive prostate cancer, which do not fall into high-risk or high-volume categories Exclusion Criteria: Patients with high-volume metastatic hormone-sensitive prostate cancer, defined by the presence of visceral metastases or four or more bone lesions with at least one beyond the vertebral bodies and pelvis Patients with high-risk metastatic hormone-sensitive prostate cancer, defined by having at least two of the three following factors - a Gleason score above 7, having at least 3 bone metastasis or presence of measurable visceral metastasis Presence of brain metastasis Use of bisphosphonate or denosumab within 28 days prior to randomization Use of older anti-androgens, including flutamide and bicalutamide, for flare protection, within 28 days prior to randomization Prior use of chemotherapy, immunotherapy, radiopharmaceutical agents, CYP17 inhibitors (e.g. abiraterone acetate), enzalutamide or apalutamide for the treatment of prostate cancer or prior participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis History of seizure or any condition that may predispose to seizure (e.g., neurological disorder, prior cortical stroke or significant brain trauma) Use of an investigational agent within 4 weeks of randomization Hypersensitivity reaction to the active pharmaceutical ingredient Clinically significant cardiovascular disease including the following: Myocardial infarction within 6 months before screening; Uncontrolled angina within 3 months before screening; Congestive heart failure New York Heart Association class 3 or 4, or a history of congestive heart failure New York Heart Association class 3 or 4, unless a screening echocardiogram or multigated acquisition scan performed within 3 months before randomization demonstrates a left ventricular ejection fraction ≥ 50%; History of clinically significant ventricular arrhythmias (e.g. sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes); History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place; Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening; Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening electrocardiogram and on physical examination; Uncontrolled hypertension as indicated by systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within 3 months before randomization) Major surgery within 28 days of randomization Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of the investigator

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Apalutamide followed by Enzalutamide Study participants will receive 12 weeks of oral apalutamide (240mg) daily, followed by five weeks of washout period, and then 12 weeks of oral enzalutamide (160mg) daily. | Drug: Apalutamide<br>* Androgen receptor inhibitor.<br>Drug: Enzalutamide<br>* Androgern receptor inhibitor<br>|
| Experimental: Group B<br>Enzalutamide followed by Apalutamide Study participants will receive 12 weeks of oral enzalutamide (160mg) daily, followed by five weeks of washout period, and then 12 weeks of oral apalutamide (240mg) daily. | Drug: Apalutamide<br>* Androgen receptor inhibitor.<br>Drug: Enzalutamide<br>* Androgern receptor inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Preference Questionnaire | This Patient Preference Questionnaire consists of 4 questions, assessing the patients preference on Apalutamide verse Enzalutamide, the factors that had an influence on their treatment preference, the most important reason for their preference and the side effect of first treatment and second treatment. | Week 29 (at the end of second treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The side effect profile as assessed Patient Preference Questionnaire | In Patient Preference Questionnaire, participants completed a sideffect checklist. | Baseline to week 29 (the end of the study) | 
| Physician Preference Questionnaire | This Physician Preference Questionnaire consists of 3 questions, assessing the physicians preference on Apalutamide verse Enzalutamide, the factors that had an influence on their treatment preference, the most important reason for their preference. | Week 29 (at the end of second treatment) | 
| Caregiver Preference Questionnaire | This Caregiver Preference Questionnaire consists of 3 questions, assessing the caregivers preference on Apalutamide verse Enzalutamide, the factors that had an influence on their treatment preference, the most important reason for their preference. | Week 29 (at the end of second treatment) | 
| The Functional Assessment of Cancer Therapy-Prostate Questionnaire (FACT-P) | This is a 39-item questionnaire assessing five domains including Physical Well-Being, Social and Family Well-Being, Emotional Well-Being, Functional Well-Being and Prostate Cancer Subscale.The higher the score, the better the QOL | Week 0 (before start of first treatment period), Week 12 (end of first treatment period), week 17 (before start of second treatment period) and Week 29 (end of second treatment period). | 
| Quality of life measured by EurolQol instrument (EQ-5D-5L) | This questionnaire consists of two parts, namely the EQ-5D-5L Descriptive System and the EQ Visual Analog Scale, the higher the score the better in quality of life | Week 0 (before start of first treatment period), Week 12 (end of first treatment period), week 17 (before start of second treatment period) and Week 29 (end of second treatment period | 
| FACT-Cognitive Function Version 3 (FACT-Cog) | This is a well-established 37-item questionnaire assessing patients' perceived cognitive impairments, perceived cognitive abilities, noticeability or comments from others, and impact of cognitive changes on quality of life. The higher the score, the better the QOL. | Week 0 (before start of first treatment period), Week 12 (end of first treatment period), week 17 (before start of second treatment period) and Week 29 (end of second treatment period | 
| Brief Fatigue Inventory (BFI) | This is a well-established 9-item questionnaire assessing patients' degree of fatigue.The higher the score, the higher fatigue level | Week 0 (before start of first treatment period), Week 12 (end of first treatment period), week 17 (before start of second treatment period) and Week 29 (end of second treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patient Preference