A Phase I/Ib, Multicentre, Study Comprising a Safety Run-In of AZD5363 when Combined with Paclitaxel in Patients with Advanced or Metastatic Breast Cancer; Followed by a Randomised Expansion of AZD5363 when Combined with Paclitaxel vs. Paclitaxel plus Placebo in Patients with ER-Positive Advanced or Metastatic Breast Cancer, Stratified by PIK3CA Mutation Status (BEECH).

Withdrawn

Conditions: breast cancer
Mamma carcinoma
10006291

Registration Number: NL-OMON37581

Lead Sponsor: Astra Zeneca

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 2

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

* 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part A: To assess the safety and tolerability of two schedules of AZD5363<br /><br>(continuous and intermittent dosing) when combined with weekly paclitaxel in<br /><br>patients with advanced or metastatic breast cancer; and to recommend, by<br /><br>assessment of dose limiting toxicities and other safety, tolerability,<br /><br>pharmacokinetic and pharmacodynamic data, a dose and schedule of AZD5363 for<br /><br>further study when combined with weekly paclitaxel.<br /><br><br /><br>Part B: To assess the relative anti-tumour activity of AZD5363 when combined<br /><br>with weekly paclitaxel vs. weekly paclitaxel plus placebo by comparison of<br /><br>change in tumour size at 12 weeks (target lesion assessment using RECIST 1.1)<br /><br>in the overall advanced or metastatic Estrogen Receptor positive breast cancer<br /><br>population and in a Phosphoinositide 3-kinase (PIK3CA) mutation-positive<br /><br>sub-population.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Part A: To make a preliminary assessment of the anti-tumour activity of AZD5363<br /><br>when combined with paclitaxel.<br /><br><br /><br>Part B:<br /><br>* To assess the relative efficacy of AZD5363 when combined with weekly<br /><br>paclitaxel compared with weekly paclitaxel plus placebo.<br /><br>* To assess the safety and tolerability of AZD5363 when combined with weekly<br /><br>paclitaxel compared with weekly paclitaxel plus placebo.<br /><br>* To investigate the effect on patients* quality of life of AZD5363 when<br /><br>combined with weekly paclitaxel, compared with weekly paclitaxel plus placebo.<br /><br><br /><br>Parts A and B:<br /><br>* To assess the pharmacokinetics of AZD5363 when combined with paclitaxel.<br /><br>To assess the pharmacokinetics of paclitaxel alone and when combined with<br /><br>AZD5363.<br /><br> To assess the pharmacokinetic/pharmacodynamic relationship.</p><br>