A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Abiraterone Versus Placebo + Abiraterone as Treatment for Patients in patients with newly diagnosed, previously untreated Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Characterised by Phosphatase and Tensin Homolog (PTEN) biomarker deficiency (CAPItello-281)
- Conditions
- Metastatic Hormone-Sensitive Prostate CancerMedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000346-33-DE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 1000
- Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic hormone-sensitive prostate adenocarcinoma without small-cell tumours
- 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
- 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
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
-Radiotherapy with a wide field of radiation within 4weeks(wks) before start of study treatment (capivasertib/placebo)
-Major surgery (excl.placement of vascular access,transurethral resection of prostate,bilateral orchiectomy,internal stents) within 4wks 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 least 4wks 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 from triplicate ECGs
ii.Any clinically important abnormalities in conduction or morphology of resting ECG
iii.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 prolong the QT interval
iv. Experience of any of the following procedures or conditions in the preceding 3 months: coronary artery bypass graft, angioplasty, myocardial infarction, or unstable angina pectoris.
v. Congestive heart failure New York Heart Association (NYHA) Grade = 2.
vi.Symptomatic hypotension - systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg
vii.Uncontrolled hypertension (SBP =160 mmHg or DBP =95 mmHg) with clinical symptoms of haemodynamic instability.
-Clinically significant abnormalities of glucose metabolism as defined by any of the following:
i.Patients with diabetes mellitus (DS) type 1 or DS type 2 requiring insulin treatment
ii.HbA1c =8.0% (63.9 mmol/mol)
-Inadequate bone marrow reserve or organ function
-As judged by the investigator,any evidence of severe or uncontrolled systemic diseases,including active bleeding diatheses,or known active infection including hepatitis B and 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 disease = 2 years. before the first dose of study intervention and of low potential risk for recurrence.Exceptions include adequately resected non-melanoma cancer and curatively treated in situ disease.
-Treatment with any of the following:
i.Nitrosourea or mitomycin C within 6wks of t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method