breast cancer Mamma carcinoma
Conditions
Interventions
Part A: Cycles of 4 weeks in which a weekly infusion of paclitaxel is
administered during the first 3 weeks. AZD5363 capsules are taken twice daily
according to a continuous or intermittent dosing s
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Provision of informed consent * Female patients * Aged at least 18 years * Histological or cytological confirmation of breast cancer with evidence of advanced or metastatic disease (must be ER+ve in Part B) * World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks * Minimum life expectancy of 12 weeks
Exclusion criteria
Exclusion criteria: * Clinically significant abnormalities of glucose metabolism;* Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids);* Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV;* Any prior exposure to agents which inhibit AKT as the primary phamacological activity;Part A: more than two prior courses of chemotherapy (including taxanes) for advanced or metastatic breast cancer.;Part B: any prior chemotherapy for advanced or metastatic breast cancer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: To assess the safety and tolerability of two schedules of AZD5363 (continuous and intermittent dosing) when combined with weekly paclitaxel in patients with advanced or metastatic breast cancer; and to recommend, by assessment of dose limiting toxicities and other safety, tolerability, pharmacokinetic and pharmacodynamic data, a dose and schedule of AZD5363 for further study when combined with weekly paclitaxel. Part B: To assess the relative anti-tumour activity of AZD5363 when combined with weekly paclitaxel vs. weekly paclitaxel plus placebo by comparison of change in tumour size at 12 weeks (target lesion assessment using RECIST 1.1) in the overall advanced or metastatic Estrogen Receptor positive breast cancer population and in a Phosphoinositide 3-kinase (PIK3CA) mutation-positive sub-population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: To make a preliminary assessment of the anti-tumour activity of AZD5363 when combined with paclitaxel. Part B: * To assess the relative efficacy of AZD5363 when combined with weekly paclitaxel compared with weekly paclitaxel plus placebo. * To assess the safety and tolerability of AZD5363 when combined with weekly paclitaxel compared with weekly paclitaxel plus placebo. * To investigate the effect on patients* quality of life of AZD5363 when combined with weekly paclitaxel, compared with weekly paclitaxel plus placebo. Parts A and B: * To assess the pharmacokinetics of AZD5363 when combined with paclitaxel. *To assess the pharmacokinetics of paclitaxel alone and when combined with AZD5363. * To assess the pharmacokinetic/pharmacodynamic relationship. | — |
Countries
Netherlands
Outcome results
None listed