Overview

Capivasertib+Abiraterone as Treatment for Patients With Metastatic Hormone-sensitive Prostate Cancer and PTEN Deficiency

Status:
Recruiting
Trial end date:
2025-11-11
Target enrollment:
0
Participant gender:
Male
Summary
This study will assess the efficacy and safety of capivasertib plus abiraterone (+prednisone/prednisolone) plus androgen deprivation therapy (ADT) versus placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC whose tumours are characterised by PTEN deficiency. The intention of the study is to demonstrate that in participants with mHSPC, the combination of capivasertib plus abiraterone (+prednisone/prednisolone) plus ADT is superior to placebo plus abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC characterised by PTEN deficiency with respect to radiographic progression-free survival (rPFS) per 1) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue and/or Prostate Cancer Working Group (PCWG3) for bone as assessed by the investigator 2) death due to any cause.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AstraZeneca
Treatments:
Abiraterone Acetate
Criteria
Inclusion Criteria:

- Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic
hormone-sensitive prostate adenocarcinoma without small-cell tumours

- 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 3 months 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

- 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 within 4 weeks before the start of study
treatment (capivasertib/placebo)

- 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 3 consecutive
ECGs ii. Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG (eg, complete left bundle branch block, third-degree heart block) iii. Any
factors that increase the risk of QTc prolongation or risk of arrhythmic events such
as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT
syndrome, family history of long QT syndrome or unexplained sudden death under 40
years of age, or any concomitant medication known to prolong the QT interval iv.
Clinically significant heart disease as evidenced by myocardial infarction, or
arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA or
Class II to IV heart failure or cardiac ejection fraction measurement of < 50% v.
Experience of any of the following procedures or conditions in the preceding 6 months:
coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction,
angina pectoris, congestive heart failure NYHA Grade ≥ 2 vi. Uncontrolled hypotension
- systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50
mmHg vii. Cardiac ejection fraction outside institutional range of normal or <50%
(whichever is higher) as measured by echocardiogram (or multiple-gated acquisition
[MUGA] scan if an echocardiogram cannot be performed or is inconclusive) viii.
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 109/L ii. Platelet count < 100x 109/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 > 1.5x ULN concurrent with
creatinine clearance < 50 mL/min (measured or calculated by Cockcroft and Gault
equation); confirmation of creatinine clearance is only required when creatinine is >
1.5x ULN

- 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

- Known additional malignancy that has had progression or has required active treatment
in the last 3 years. Exceptions include basal cell carcinoma of the skin, and squamous
cell carcinoma of the skin that has undergone potentially curative therapy

- 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. Potent inhibitors or inducers of CYP3A4 within 2 weeks before the start
of study treatment (3 weeks for St John's wort), or sensitive substrates of CYP3A4,
CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week before the start
of study treatment

- Drugs known to prolong the QT interval within 5 half-lives of the first dose of study
treatment

- History of hypersensitivity to active or inactive excipients of capivasertib,
abiraterone, or drugs with a similar chemical structure or class

- Any restriction or contraindication based on the local prescribing information that
would prohibit the use of abiraterone