Triple-negative Breast Cancer
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed TNBC from most recenty collected tumour tissue sample 2. Metastatic or locally recurrent disease; locally recurrent disease most not be amenable to resection with curative intent (patient who are considered suitble for surgical or ablative techniques following potential down-staging with study treatment are not eligible) 3. ECOG/WHO PS: 0-1 4. Measurable disease according to RECIST 1.1 and/or lytics or mixed bone lesions that can be assessed by CT or MRI in the absence of measurable disease 5. FFPE tumour sample from primary/recurrent cancer 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 640 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: 1. Prior chemotherapy in the (neo)adjuvant setting within 12 months from the end of chemotherapy to inclusion into this study 2. Prior systematic therapy for inoperable locally advanced or metastatic disease 3. Prior treatment with any of the following: - AKT, PI3K, and/or mTOR inhibitors - Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study) - 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) as agreed by the sponsor - Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose 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 prior to the first dose of study treatment. 4. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo) 5. Pre-existing sensory or motor polyneuropathy =grade 2 according to NCI CTCAE v5 6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment 7. Any of the following cardiac criteria at screening: -Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs -Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block) -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 -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 New York Heart Association (NYHA) grade =2 -Uncontrolled hypotension – SBP <90 mmHg and/or DBP <50 mmHg -Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiplegated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive). 8. Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening: -Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment -HbA1c =8.0% (63.9 mmol/mol) 9. Inadequate bone marrow reserve or organ function at screening 10. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by investigator assessment of PFS (progression-free survival) in patients with PI3K/AKT/PTEN pathway-altered tumours, and OS (overall survival) in the overall population and pathway-altered subgroup.;Secondary Objective: For overall population and pathway-altered subgroup: 1. To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by investigator assessment of PFS2 2.To further assess the efficacy of capivasertib + with paclitaxel versus placebo + paclitaxel by assessment of ORR, DoR, CBR 3.To evaluate the safety and tolerability of capivasertib + paclitaxel vs placebo + paclitaxel 4.To assess the impact of capivasertib + paclitaxel vs placebo + paclitaxel on patients’ disease-related symptoms, physical function, and HRQoL For overall population: 5. To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by investigator assessment of PFS 6.To evaluate the PK of capivasertib including the influence of intrinsic and extrinsic patient factors;Primary end point(s): 1. Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1) 2. Overall Survival;Timepoint(s) of evaluation of this end point: 1. The time from date of randomisation to the date of progression or death due to any cause. 2. The time from date of randomisation to the date of death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Investigator assessment of PFS2 2. Response Rate (ORR) - percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1) Duration of Response (DoR) - time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression ,and Clinical Benefit Rate (CBR) - number of patients with complete or partial response or with stable disease maintained =24 weeks (as assessed by the investigator, using RECIST 1.1) divided by the number of patients in the analysis. 3. AEs/SAEs; vital signs; collection of clinical chemistry, haematology, glucose metabolism parameters; ECGs parameters. 4. Plasma PK parameters derived from a population PK model of plasma concentrations and patient factors 5. EORTC QLQ BR23 (EORTC Quality of Life Questionnaire breast cancer specific module) and EORTC QLQ C30 (EORTC Quality of Life Questionnaire Core 30 items) scale/item scores;Timepoint(s) of evaluation of this end point: 1. Time from randomization to second progression or death due to any cause 2. Every 8 weeks 3. The overall duration of the study 4. During months 1 and 2. 5. Periodically until withdrawal | — |
Countries
Argentina, Brazil, Canada, China, Czech Republic, France, Greece, Hungary, India, Japan, Korea, Republic of, Mexico, Philippines, Poland, Portugal, Russian Federation, Saudi Arabia, Slovakia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactInformation center
AstraZeneca
Outcome results
None listed