A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib+Abiraterone Versus Placebo+Abiraterone as Treatment for Patients With DeNovo Metastatic Hormone-Sensitive Prostate Cancer Characterised by PTEN Deficiency.

AstraZeneca1 site in 1 country1,012 target enrollmentJuly 13, 2020

ConditionsHormone-Sensitive Prostate Cancer

InterventionsCapivasertib Abiraterone Acetate Placebo

Overview

Phase: Phase 3
Intervention: Capivasertib
Conditions: Hormone-Sensitive Prostate Cancer
Sponsor: AstraZeneca
Enrollment: 1012
Locations: 1
Primary Endpoint: Radiographic Progression-free Survival (rPFS)
Status: Active, not recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

July 13, 2020

End Date

March 29, 2027

Last Updated

3 months ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

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

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).

Arms & Interventions

Capivasertib + Abiraterone

Participants receive capivasertib in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Intervention: Capivasertib

Capivasertib + Abiraterone

Participants receive capivasertib in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Intervention: Abiraterone Acetate

Placebo + Abiraterone

Participants receive placebo in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Intervention: Placebo

Placebo + Abiraterone

Participants receive placebo in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Intervention: Abiraterone Acetate

Outcomes

Primary Outcomes

Radiographic Progression-free Survival (rPFS)

Time Frame: Up to approximately 55 months

rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone, or death due to any cause for each study arm.

Secondary Outcomes

Overall survival (OS)(Up to approximately 80 months)
Time to Pain Progression (TTPP)(Up to approximately 80 months)
Time to PSA progression(Up to approximately 55 months)
Time To Castration Resistance (TTCR)(Up to approximately 80 months)
Overall Pain Severity and Pain Interference as assessed by BPI-SF questionnaire(Up to approximately 80 months)
Fatigue intensity, severity and interference domains assessed by the Brief Fatigue Inventory (BFI)(Up to approximately 80 months)
Plasma concentration of capivasertib 1h post-dose(Cycle 1 Day 1)
Time to Start of First Subsequent Therapy or Death (TFST)(Up to approximately 55 months)
Symptomatic Skeletal Event-Free Survival (SSE-FS)(Up to approximately 80 months)
Plasma concentration of capivasertib pre-dose(Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15)
Disease-Related Symptoms and HRQoL using the Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P) questionnaire(Up to approximately 80 months)
Progression-Free Survival after next-line treatment (PFS2)(Up to approximately 80 months)
Plasma concentration of capivasertib 4h post-dose(Cycle 1 Day 1)