Gender
Male
Age Group
18 Years to 130 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Asymptomatic or mildly symptomatic, histologically-confirmed de novo hormone-sensitive
prostate adenocarcinoma without small-cell tumours diagnosed within 180 days of
randomisation
- Consent to provide a FFPE tissue block (preferred) or slides. Tissue from bone
metastases is not acceptable
- A valid PTEN IHC result indicating PTEN deficiency (centralized testing)
- Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone
lesion and/or ≥ 1 soft tissue lesion accurately assessed at baseline and suitable for
repeated assessment with CT and/or MRI. PSMA PET identification only will not be
eligible
- Candidate for abiraterone and steroid therapy
- Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral
orchiectomy (regardless of method) is from 0 days to a max. of 93 days prior to
randomisation
- Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0 to 1 with no
deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
- Able and willing to swallow and retain oral medication
- 7-day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory(BFI)
questionnaires and the analgesic diary during screening completed. Participants must
complete a minimum of 4 successful assessments within a 7-day period prior to
randomisation.
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm
- Capable of giving signed informed consent
- Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples
Exclusion Criteria:
- Prior radical prostatectomy or definitive radiotherapy with therapeutic intent for
prostate cancer. Palliative radiotherapy is allowed providing any wide field radiation
therapy is completed more than 4 weeks before the start of study treatment
- Major surgery (excluding placement of vascular access, transurethral resection of
prostate, bilateral orchiectomy, or internal stents) within 4 weeks of the 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)
- Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis which required steroid treatment, or any evidence of
clinically active interstitial lung disease
- Any of the following cardiac criteria:
i. Mean resting corrected QT interval (QTc) > 470 msec obtained from triplicate ECGs
ii. History of QT prolongation associated with other medications that required
discontinuation of that medication.
iii. Family history of long QT syndrome, or unexplained sudden death under 40 years of age
in first-degree relatives.
iv. Medical history significant for arrhythmia which is symptomatic or requires treatment,
symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic
sustained ventricular tachycardia.
v. Any clinically important abnormalities in conduction or morphology of resting ECG (eg,
complete left bundle branch block, third-degree heart block) vi. Any factors that increase
the risk of QTc prolongation or risk of arrhythmic events such as hypokalaemia, potential
for torsades de pointes, congenital long QT syndrome, or any concomitant medication known
to significantly prolong the QT interval vii. Experience of any of the following procedures
or conditions in the preceding 3 months: coronary artery bypass graft, angioplasty,
myocardial infarction, angina pectoris.
viii. Congestive heart failure NYHA Grade ≥ 2 ix. Symptomatic hypotension - systolic blood
pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50 mmHg x. Uncontrolled
hypertension (SBP ≥ 160 mmHg or DBP ≥ 95 mmHg).
- Clinically significant abnormalities of glucose metabolism as defined by any of the
following:
i. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring
insulin treatment ii. HbA1c ≥8.0% (63.9 mmol/mol)
- Inadequate bone marrow reserve or organ function as demonstrated by any of the
following laboratory values:
i. Absolute neutrophil count < 1.5x 10^9/L ii. Platelet count < 100x 10^9/L iii.
Haemoglobin < 9 g/dL (< 5.59 mmol/L) iv. Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) > 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
(measured or calculated by Cockcroft and Gault equation)
- As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases, including active bleeding diatheses, or known active infection including
hepatitis B, hepatitis C, and HIV
- unevaluable for both bone and soft tissue progression as defined by meeting both of
the following criteria: i. a "superscan" of bone scan, and ii. no soft tissue lesion
that can be assessed by RECIST criteria
- 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, metabolic dysfunction, 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 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 include adequately
resected non-melanoma skin cancer and curatively treated in situ disease.
- Treatment with any of the following:
i. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment ii.
Any investigational agents or study drugs from a previous clinical study within 30
days or 5 half-lives (whichever is longer) of the first dose of study treatment iii.
Any other chemotherapy, immunotherapy, immunosuppressant medication (other than
corticosteroids) or anticancer agents within 3 weeks of the first dose of study
treatment. A longer washout may be required for drugs with a long half-life (eg,
biologics) iv. Strong inhibitors or strong inducers of CYP3A4 within 2 weeks before
the start of study treatment (3 weeks for St John's wort). Note that adequate washout
or dose reduction may be required for some CYP3A substrates prior to initiating
Capivasertib dosing.
- Drugs known to significantly prolong the QT interval and associated with Torsades de
Pointes within 5 half-lives of the first dose of study treatment
- Participation in another clinical study with an investigational product administered
in the last 30 days or 5 half-lives, whichever is longer.
- History of hypersensitivity to active or inactive excipients of capivasertib,
abiraterone, or drugs with a similar chemical structure or class.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
- Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
- Any restriction or contraindication based on the local prescribing information that
would prohibit the use of abiraterone.