A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Phase 3

• Conditions: Prostate Cancer

• Registration Number: NL-OMON53734
• Lead Sponsor: Astra Zeneca

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 7

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

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<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 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<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 informed consent -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 adequately resected non-melanoma skin
cancer and curatively treated in situ disease - Persistent toxicities(CTCAE
Grade >=2)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The purpose of this study is to evaluate the efficacy and safety of<br /><br>capivasertib in addition to docetaxel versus placebo plus docetaxel in patients<br /><br>with mCRPC.<br /><br><br /><br>Primary objective is to demonstrate superiority of capivasertib + docetaxel<br /><br>relative to placebo + docetaxel by assessment of overall survival (OS) in<br /><br>patients with mCRPC in the overall population.<br /><br><br /><br>See Section 3 of the Protocol AM1</p><br>