Capivasertib+Abiraterone as Treatment for Patients With Metastatic Hormone-sensitive Prostate Cancer and PTEN Deficiency (CAPItello-281)

  • STATUS
    Recruiting
  • End date
    Nov 11, 2025
  • participants needed
    1000
  • sponsor
    AstraZeneca
Updated on 28 May 2022

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.

Details
Condition Hormone-Sensitive Prostate Cancer
Treatment Placebo, abiraterone acetate, Capivasertib
Clinical Study IdentifierNCT04493853
SponsorAstraZeneca
Last Modified on28 May 2022

Eligibility

Yes No Not Sure

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
-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
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
following laboratory values
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
i. Absolute neutrophil count < 1.5x 109/L ii. Platelet count < 100x 109/L iii
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
Haemoglobin < 9 g/dL (< 5.59 mmol/L) iv. Alanine aminotransferase (ALT) and
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
aspartate aminotransferase (AST) > 2.5x upper limit of normal (ULN) if no
Evidence of dementia, altered mental status, or any psychiatric condition that would prohibit understanding or rendering of informed consent
demonstrable liver metastases or > 5x ULN in the presence of liver metastases
Previous allogeneic bone marrow transplant or solid organ transplant
Elevated alkaline phosphatase (ALP) is not exclusionary if due to the presence
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
of bone metastases and liver function is otherwise considered adequate in the
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
investigator's judgement v. Total bilirubin > 1.5x ULN (participants with
Drugs known to prolong the QT interval within 5 half-lives of the first dose of study treatment
confirmed Gilbert's syndrome may be included in the study with a higher value)
History of hypersensitivity to active or inactive excipients of capivasertib, abiraterone, or drugs with a similar chemical structure or class
vi. Creatinine > 1.5x ULN concurrent with creatinine clearance < 50 mL/min
Any restriction or contraindication based on the local prescribing information that would prohibit the use of abiraterone
(measured or calculated by Cockcroft and Gault equation); confirmation of
creatinine clearance is only required when creatinine is > 1.5x ULN
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