Metastatic Castration Resistant Prostate Cancer
Conditions
Interventions
Capivasertib: 320 mg (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle. Number of Cy
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Histologically-confirmed prostate adenocarcinoma without neuroendocrine or small cell cancers - Metastatic disease documented prior to randomisation by clear evidence of 1 bone lesion or more (defined as 1 lesion with positive uptake on bone scan) and/or 1 soft tissue lesion or more (measurable or non-measurable) - Patient must have been previously treated with a next generation hormonal agent (NHA), ie, abiraterone, enzalutamide, apalutamide or darolutamide, for prostate cancer for at least 3 months and shown evidence of disease progression (radiological or via PSA assessment) while receiving the NHA - Evidence of mCRPC with progression of disease despite androgen deprivation therapy (ADT) and after anti-androgen withdrawal if applicable - Serum testosterone level 50 ng/dL or less - Candidate for docetaxel and steroid therapy - Ongoing ADT with LHRH agonist, LHRH antagonist, or bilateral orchiectomy - Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1 and anticipated minimum life expectancy of 12 weeks - Confirmation that archival formalin-fixed paraffin-embedded (FFPE) tumour tissue sample which meets the minimum pathology and sample requirements is available to send to the central laboratory - Able and willing to swallow and retain oral medication - Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion criteria
Exclusion criteria: - Radiotherapy with a wide field of radiation within 4 weeks before start of study treatment - Major surgery (excl. placement of vascular access, transurethral resection of prostate, bilateral orchiectomy, internal stents) within 4 weeks of start of study treatment - Brain metastases,or spinal cord compression (unless spinal cord compression is asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment) - Any of the following cardiac criteria: i. Mean resting corrected QT interval (QTc) >470 msec from 3 consecutive ECGs ii. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG iii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age,or any concomitant medication known to prolong the QT interval iv. Experience of any of the following procedures or conditions in the preceding 6months: coronary artery bypass graft, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade 2 or less. v. Uncontrolled hypotension - systolic blood pressure 2.5x upper limit of normal (ULN) if no demonstrable liver metastases or > 5x ULN in the presence of liver metastases. Elevated alkaline phosphatase (ALP) is not exclusionary if due to the presence of bone metastases and liver function is otherwise considered adequate in the investigator's judgement v. Total bilirubin > 1.5x ULN (participants with confirmed Gilbert's syndrome may be included in the study with a higher value) vi. Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula without the need for chronic dialysis; - As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), which, in the investigator's opinion, makes it undesirable for the patient to participate in the study or that would jeopardise compliance with the protocol. - Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib - Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contra-indicates the use of an investigation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) [ Time Frame: up to approximately 52 months ] Overall survival is defined as time from randomisation until the date of death due to any cause. | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Czech Republic, France, Greece, Hungary, India, Japan, Mexico, Netherland, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed