Investigating Safety, Tolerability and Efficacy of AZD5363 When Combined With Paclitaxel in Breast Cancer Patients
Summary
The purpose of this study is to investigate the safety and efficacy of different doses and schedules of AZD5363, when in combination with paclitaxel, in treatment of patients with advanced or metastatic breast cancer. Also to investigate a selected dose and schedule of AZD5363 in combination with paclitaxel vs. paclitaxel in combination with placebo in treatment of patients with estrogen receptor-positive advanced or metastatic breast cancer, including a subgroup who have the phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) tumour mutation.
Timeline
- Start
- 2012-10-03
- Primary completion
- 2017-01-28
- Completion
- 2022-10-03
Outcome
Missed primary endpoint
registry analysis (superiority test); Part B AZD5363 vs Part B Placebo; p = 0.308; Hazard Ratio (HR) 0.80 (80% CI 0.60 to 1.06); Regression, Cox; note: 2-sided p-value NCT01625286 ↗
paper Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2- advanced/metastatic breast cancer patients. PMID 30860570 ↗
Publications
- Hrebien S, Citi V, Garcia-Murillas I, Cutts R, Fenwick K, Kozarewa I, McEwen R, Ratnayake J, Maudsley R, Carr TH, de Bruin EC, Schiavon G, Oliveira M, Turner N. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol. 2019 Jun 1;30(6):945-952. doi: 10.1093/annonc/mdz085.
- Turner NC, Alarcon E, Armstrong AC, Philco M, Lopez Chuken YA, Sablin MP, Tamura K, Gomez Villanueva A, Perez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 2019 May 1;30(5):774-780. doi: 10.1093/annonc/mdz086.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Capivasertib | Small molecule | 400 mg | Oral |
| Background | Paclitaxel | Small molecule | 90 mg/m2 | Intravenous |