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STAGE 1 ONLY AZD5363 480mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

STAGE 1 ONLY Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

STAGE 2 AZD5363 360mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

STAGE 2 AZD5363 240mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

Stage 1: AZD5363 480mg or placebo twice daily oral dosing for 4 and 1/2 days (9 doses) Stage 2: AZD5363 360mg or 240mg daily oral dosing for 4 and 1/2 days (9 doses)

AZD5363

John FR Robertson, MD

To compare the effect of four and a half days treatment of a range of doses of AZD5363 on selected markers of the AKT pathway and anti-proliferation compared with placebo in oestrogen receptor positive breast cancers.

To assess the tolerability of four and a half days treatment of AZD5363.

The principal research questions to be addressed are whether (or not) AZD5363 is "hitting its therapeutic target" sufficiently and to the extent that is required to produce efficacy in pre-clinical experiments.

The primary endpoint markers have been selected to determine this.

Reductions in markers of the AKT pathway and increases in markers of anti-proliferation will characterise the degree of biological activity arising from the inhibition of AKT across a range of doses of AZD5363.

AKT Inhibitor in Oestrogen Positive Breast Cancer

The Short Term Effects of an AKT Inhibitor (AZD5363) on Biomarkers of the AKT Pathway and Anti-tumour Activity in a Breast Cancer Paired Biopsy Study

By measuring biological changes in the tumour and circulation via measurement of changes in alternative biological markers which relate to the AKT pathway:

Tumour total and pAKT Tumour: cleaved caspase 3; pS6 (IHC); FOXO3a Blood (platelet-rich plasma): Total and pPRAS40; Total and pGSK3b; Total and pAKT.

Tolerability and toxicity will be measured following short term exposure to AZD5363 by incidence and severity of adverse events.

Participants will be monitored for adverse events during the study and for at least 30 days after the end of treatment.

Analysis of toxicity following the completion of Stage 1, taking into consideration that Stage 2 will use lower doses of AZD5363, and at the end of Stage 2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
AKT Inhibitor in Oestrogen Positive Breast Cancer	NCT02077569	Invasive Breast...	AZD5363	18 Years -	University of Nottingham
AKT Inhibitor in Oestrogen Positive Breast Cancer	NCT02077569	Invasive Breast...	AZD5363	18 Years -	University of Nottingham

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