Metastatic Castrate Resistant Prostate Cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Xtandi
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ENZALUTAMIDE
CAS Number: 915087-33-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Sponsors
Astellas Pharma Europe Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Age 18 or older; 2. Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable); 3. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features; 4. Ongoing ADT with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of initiation of IMP, or bilateral orchiectomy (i.e., surgical or medical castration); 5. Serum testosterone level = 1.73 nmol/L (= 50 ng/dL); 6. Metastatic (M1) disease documented by at least 2 bone lesions on bone scan, or soft tissue disease documented by CT/MRI; 7. Progressive disease at study entry defined as the following occurring in the setting of castrate levels of testosterone: PSA progression defined by a minimum of three rising PSA levels with an interval of = 1 week between each determination. The PSA value at Screening should be = 2 µg/L (= 2 ng/mL). In the event of prior androgen receptor inhibitor use, the most recent local PSA and the Screening PSA assessed by the central laboratory (central PSA) must be obtained at least 4 weeks after the last dose of androgen receptor inhibitor; 8. Asymptomatic or minimally symptomatic prostate cancer (BPI SF question 3 score of =65 years) yes F.1.3.1 Number of subjects for this age range 475
Exclusion criteria
Exclusion criteria: 1. Absolute neutrophil count (ANC) upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 times ULN; Child-Pugh B and C hepatic impairment; 3. Creatinine > 177 µmol/L (> 2 mg/dL); 4. Albumin = 30 g/L (= 3.0 g/dL; 5. Prior treatment with the following agents for the treatment of prostate cancer: Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory therapies (e.g. Sipuleucel-T, DCVAC); Cytotoxic chemotherapy (e.g. docetaxel, cabazitaxel, mitoxantrone, estramustine); Participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (e.g. ARN-509, ODM-201, VT-464; unless the treatment was placebo); 6. Current or prior treatment within 4 weeks prior to initiation of IMP with the following agents for the treatment of prostate cancer: Antiandrogens (e.g., bicalutamide, nilutamide, flutamide); 5-a reductase inhibitors (e.g., finasteride, dutasteride); Estrogens; Anabolic steroids; Drugs with antiandrogenic properties such as spironolactone > 50 mg/kg; Progestational agents; 7. Subject has received investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to initiation of IMP; 8. Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to initiation of IMP; 9. Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation of IMP; 10. Major surgery within 4 weeks prior to initiation of IMP; 11. History of seizure or any condition that may predispose to seizures at any time in the past (e.g., prior cortical stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). History of loss of consciousness or transient ischemic attack within 12 months prior to Screening; 12. Known or suspected brain metastasis or active leptomeningeal disease; 13. History of another malignancy within the previous 5 years other than non-melanoma skin cancer; 14. Clinically significant cardiovascular disease including: Myocardial infarction within six months prior to Screening; Uncontrolled angina within three months prior to Screening; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is = 45%; History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes); History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; Bradycardia as indicated by a heart rate 170 mmHg or diastolic blood pressure > 105 mmHg at Screening; 15. Gastrointestinal disorders affecting absorption (e.g., extensive small bowel resection, active inflammatory bowel disease); 16. Medical contraindications to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of continuing treatment with enzalutamide after adding docetaxel and prednisolone versus placebo plus docetaxel and prednisolone, as measured by progression-free survival (PFS) in subjects with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with progression during treatment with enzalutamide alone;Secondary Objective: To evaluate the effect of continuing treatment with enzalutamide after adding docetaxel and prednisolone versus placebo plus docetaxel and prednisolone, as measured by the following in subjects with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with progression during treatment with enzalutamide alone: - Time to prostate-specific antigen (PSA) progression; - PSA response; - Objective response rate; - Time to pain progression; - Time to opiate use for cancer-related pain; - Time to first skeletal-related event; - Quality of life. Safety profile including cumulative dose of docetaxel and Health Resource Use will be described for these subjects.;Primary end point(s): The primary efficacy endpoint is PFS with progression defined as radiographic progression, unequivocal clinical progression, or death. PFS is defined as the time from randomization to the earliest objective evidence of radiographic progression, unequivocal clinical progression, or death on study, whichever occurs first. - Radiographic disease progression is defined for bone disease by the appearance of 2 or more new lesions on whole-body radionuclide bone scan per PCWG2 criteria or for soft tissue disease by RECIST 1.1; - Unequivocal clinical progression is defined as any of the following: - new onset cancer pain requiring chronic administration of opiate analgesic medication; - deterioration from prostate cancer of ECOG performance status score to 3 or higher; - initiation of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progress | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to PSA progression, defined as the time from randomization to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a = 25% increase and an absolute increase of = 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later; - PSA response, defined as the percentage change in PSA from randomization to Week 13 (or earlier for those that discontinue therapy), as well as the maximum decline in PSA that occurs at any point after treatment; - Objective response rate, defined as the best overall radiographic response after randomization as per Investigator assessments of response for soft tissue disease per RECIST 1.1, in subjects who have a measurable tumor; - Time to pain progression, defined as the time to an increase of = 30% from randomization in the mean of BPI-SF pain intensity item scores (items 3, 4, 5, and 6); - Time to opiate use for cancer-related pain, defined as the time to initiation of chronic administration of opiate analgesia; - Time to first SRE, defined as the time from randomization to radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain; - Quality of life, as assessed using FACT-P and EQ-5D-5L. Other Endpoints: - Cumulative dose of docetaxel. - Health resource use (hospitalization and duration thereof; number and types of visits to a health professional) in Period 1 and Period 2. Exploratory Endpoints: - To analyze candidate biomarkers in circulation for association with response or progression and for identifying mechanisms of resistance. Safety Endpoints: - Safety in both Periods will be assessed by AEs, clinically significant changes in physical examination, vital signs, laboratory values, and ECGs. - Deaths, defined as deaths due to any cause, will be summarized d | — |
Countries
Austria, Belgium, Czechia, Czech Republic, France, Germany, Greece, Italy, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom
Contacts
Public ContactMary Mantock
Astellas Pharma Europe B.V.
Outcome results
None listed