Prostate Cancer Prostate Cancer
Conditions
Interventions
Study treatment options:
Eligible patients will be randomised in a 1:1 ratio (capivasertib + docetaxel:
placebo + docetaxel)
See section 6 of Study Protocol AM1
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Histologically-confirmed prostate adenocarcinoma without predominant neuroendocrine or small cell cancers - Metastatic disease documented prior to randomisation by clear evidence of >= 1 bone lesion (defined as 1 lesion with positive uptake on bone scan) and/or >= 1 soft tissue lesion (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) - Serum testosterone level
Exclusion criteria
Exclusion criteria: -Radiotherapy with a wide field of radiation within4 weeks before start of study treatment -Major surgery(excl.placement of vascular access,transurethral resection of prostate,bilateral orchiectomy,internal stents)within4 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 least4 weeks prior to start of study treatment) -Any of the following cardiac criteria i.Mean resting correctedQT interval(QTc)>470msec from3consecutiveECGs ii.Any clinically important abnormalities in rhythm, conduction or morphology of restingECG iii.Any factors that increase the risk ofQTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital longQTsyndrome, family history of longQT syndrome or unexplained sudden death under40years of age,orany concomitant medication known to prolong theQTinterval iv.Experience of any of the following procedures or conditions in the preceding3months: coronary artery bypass graft, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade>=2 v.Symptomatic hypotension -systolic bloodpressure=8.0%(63.9mmol/mol) -Inadequate bone marrow reserve or organ function as demonstrated by laboratory values as specified in the protocol -As judged by the investigator,any evidence of diseases(including severe or uncontrolled systemic diseases,uncontrolled hypertension, history of interstitial pneumonia/pneumonitis or interstitial disease,renal transplant and active bleeding diseases),that makes it undesirable for the patient to participate in the study or that would jeopardise compliance with the protocol - Known to have active hepatitis BorCinfection;HIVwith a CD4+ T-cell count=2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions adequately resected non-melanoma skin cancer and curatively treated in situ disease - Persistent toxicities(CTCAE Grade >=2)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The purpose of this study is to evaluate the efficacy and safety of capivasertib in addition to docetaxel versus placebo plus docetaxel in patients with mCRPC. Primary objective is to demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of overall survival (OS) in patients with mCRPC in the overall population. See Section 3 of the Protocol AM1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secundary are - To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of OS in patients with mCRPC and PTEN proficient tumours (IHC). - To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of OS in patients with mCRPC and PTEN deficient tumours (IHC). -To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of radiographic progression free survival (rPFS) in patients with mCRPC in the overall population. - To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of time to pain progression (TTPP) in patients with*mCRPC in the overall population . - To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of time to first Symptomatic Skeletal-Related Event (SSRE) in patients with* mCRPC in the overall population. See Section 3 of the Protocol AM1 | — |
Countries
Netherlands
Outcome results
None listed