Capivasertib + Abiraterone as Treatment for Patients with Metastatic Hormone-sensitive Prostate Cancer Characterised by PTEN deficiency (CAPItello-281)

You likely can't join if

• 1.Prior radical prostatectomy or definitive radiotherapy (RT) with therapeutic intent for prostate cancer. Palliative RT is allowed within 4 wks before start of study 2.Major surgery within 4 wks of start of study 3.Brain metastases, or spinal cord compression (unless asymptomatic, treated and stable 4 Past medical history or evidence of ongoing interstitial lung disease or radiation pneumonitis requiring steroids 5.Any of the following cardiac criteria: -Mean resting QTc >470 msec -History of QT prolongation associated with other medications that required discontinuation - Family history of long QT syndrome or unexplained sudden death under the age of 40 - Medical history significant for arrhythmia, symptomatic or requiring treatment; symptomatic or uncontrolled atrial fibrillation; or asymptomatic sustained ventricular tachycardia - Any clinically important abnormalities of resting ECG - Factors that increase the risk of QTc prolongation or of arrhythmic events, or any concomitant medication known to significantly prolong the QT interval and associated with Torsade de Pointes - Experience of any of the following in the preceding 3 months: coronary artery bypass graft, angioplasty, myocardial infarction or unstable angina pectoris - Congestive heart failure NYHA Grade ≥2 - Symptomatic hypotension (SBP<90 mmHg and/or DBP<50mmHg)or uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥95 mmHg) 6. Any of following clinically significant abnormalities of glucose metabolism: - Patients with diabetes mellitus type 1 or 2 requiring insulin - HbA1c ≥8.0% (63.9 mmol/mol) 7. Inadequate bone marrow reserve or organ function: - Neutrophils <1.5x109/L - Platelets <100x109/L - Hb <9g/dL (<5.59 mmol/L) - ALT and AST >2.5x ULN if no liver metastases or >5x ULN if liver metastases - Bilirubin >1.5x ULN - CrCL <50 mL/min 8. Severe or uncontrolled systemic diseases, including active bleeding diatheses, active infection including hepatitis B and C. diagnosis with HIV or a history of an AIDS opportunistic infection within the past 12 months 9. Unevaluable for both bone and soft tissue progression as defined by the following : bone "superscan" and no soft tissue lesion evaluable by RECIST 10.Conditions that would preclude adequate absorption of capivasertib
• 11. Any other clinical finding that, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug 12. Evidence of dementia, altered mental status, or any psychiatric condition prohibiting understanding or rendering of informed consent 13. Previous allogeneic bone marrow or solid organ transplant 14. History of another primary malignancy except for malignancy treated with curative intent with no known disease ≥ 2 years before starting study and of low recurrence risk 15. Following treatments: - Nitrosourea or mitomycin C within 6 wks of the start of study - Any other anticancer therapy or immunosuppressant medication (other than corticosteroids) within 3 wks of the start of study - Strong inhibitors or inducers of CYP3A4 within 2 wks before the start of study - Drugs known to prolong the QT interval and associated with torsades de pointes within 5 T½of the start of the study 16. Participation in another clinical study with an investigational product administered in the last 30 days or 5 half-lives whichever is longer 17. History of hypersensitivity to active or inactive excipients of capivasertib, abiraterone, or drugs with a similar chemical structure or class 18. Involvement in the planning and/or conduct of the study 19. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study requirements 20. Any restriction or contraindication based on the local prescribing information that would prohibit the use of abiraterone