Metastatic Castration Resistant Prostate Cancer MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 26.1 Level: PT Classification code 10062904 Term: Hormone-re
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
Male
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 = 50 ng/dL - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
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 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<90mmHg and/or diastolic bloodpressure<50mmHg vi.Haemodynamic instability -Clinically significant abnormalities of glucose metabolism as defined by any of the following i.Patients with diabetes mellitus(DM)type1 or DMtype2requiring insulin treatment ii.HbA1c=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 lung 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 a detectable viral RNA or CD4+ T-cell count<350cells/uL or a historyof an AIDS-defining opportunistic infection within the past12months -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, finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug,may affect the interpretation of the results,render the patient at high risk from treatment complications or interferes with obtaining informed consent.Evidence of dementia,altered mental status,or any psychiatric condition that would prohibit understanding or rendering of informedconsent -Previous allogeneic bone marrow transplant or solid organ transplant -History of another primary malignancy except for malignancy treated with curative intent with no known active disease=2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated insitu disease -Persistent toxicities(CTCAE Grade =2)caused by previous anticancer therapy, excluding alopecia. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of overall survival (OS) in patients with mCRPC in the overall population.;Secondary Objective: To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of: - OS in patients with mCRPC and PTEN- proficient tumours (IHC) - OS in patients with mCRPC and PTEN-deficient tumours (IHC) - radiographic progression free survival (rPFS) - time to pain progression (TTPP) - time to first Symptomatic Skeletal- Related Event (SSRE) in the overall population To demonstrate effectiveness of capivasertib + docetaxel relative to placebo + docetaxel by assessment of: - rPFS in patients with mCRPC and PTEN-proficient tumours (IHC) - rPFS in patients with mCRPC and PTEN-deficient tumours (IHC) - time to deterioration in urinary symptoms (TTDUS) - time to deterioration in Physical Functioning (TTDPF) - Health-related quality of life (HrQoL) using the BPI-SF in the overall population To evaluate the PK of capivasertib in combination with docetaxel in the overall population.;Primary end point(s): Overall survival is defined as time from randomisation until the date of death due to any cause. The comparison will include all randomised patients as randomised, regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy.;Timepoint(s) of evaluation of this end point: Time from randomisation until the date of death due to any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. OS is defined as time from randomisation until the date of death due to any cause. 2.Radiographic Progression-free Survival (rPFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST 1.1) for soft tissue and/or Prostate Cancer Working Group 3(PCWG3) for bone as Assessed by the Investigator 3. Time to pain progression (TTPP) based on a 2-point increase from baseline in the Brief Pain Inventory-Short Form (BPI-SF) Item 3 ‘worst pain in 24 hours’ score and/or initiation of/increase in opioid analgesic use 4. Time to start Symptomatic Skeletal-Related Event (SSRE) 5. Time to deterioration in urinary symptoms (TTDUS), change from baseline that reaches a clinically meaningful deterioration threshold. 6. Time to deterioration in Physical Functioning (TTDPF), change from baseline that reaches a clinically meaningful deterioration threshold. 7. Change from baseline in BPI-SF worst pain score, pain severity and interference domain scores. 8. Plasma concentration of capivasertib derived from a population PK model;Timepoint(s) of evaluation of this end point: Time from randomization to: 1.OS: until the date of death due to any cause. 2. radiographic progression per RECIST version 1.1 (soft tissue) and/or PCWG3 (bone) criteria, or death due to any cause 3. clinically meaningful pain progression increase from baseline BPI-SF and/or initiation of/increase in opioid analgesic use 4. use of radiation therapy to prevent or relieve skeletal symptoms; Occurrence of new symptomatic pathological bone fractures; Occurrence of spinal cord compression; Orthopaedic surgical intervention for bone metastasis 5. date of deterioration in EORTC, QLQ-PR25 (US) subscale scores 6. date of deterioration in EORTC, QLQ-C30 PF subscale scores 7.From baseline to post-baseline 8.Plasma concentration of capivasertib pre-and post-dose (1h, 2h, 4h) | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Czech Republic, France, Greece, Hungary, India, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed