AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer

• Assessment of safety and tolerability of AZD2014, when given in combination with fulvestrant, by assessment of: adverse events, clinical chemistry and haematology laboratory parameters, ECG data, vital signs and physical examination. [ Time Frame: From screening until the end of the follow up period, an expected average of 6 months ] [ Designated as safety issue: Yes ]
• Determination of the steady state PK profile of AZD2014 in combination with fulvestrant by assessment including:maximum plasma concentration of AZD2014 at steady state(Css,max),time to Css,max and area under the plasma concentration-time curve (AUCss). [ Time Frame: At multiple time-points on Day 22 of multiple dosing ] [ Designated as safety issue: No ]

• To assess safety and tolerability of AZD2014, when given in combination with fulvestrant, by assessment of: adverse events, clinical chemistry and haematology laboratory parameters, ECG data, vital signs and physical examination. [ Time Frame: From screening until the end of the follow up period, an expected average of 6 months ] [ Designated as safety issue: Yes ]
• To determine the steady state PK profile of AZD2014 in combination with fulvestrant by assessment including:maximum plasma concentration of AZD2014 at steady state(Css,max),time to Css,max and area under the plasma concentration-time curve (AUCss). [ Time Frame: At multiple time-points on Day 22 of multiple dosing ] [ Designated as safety issue: No ]

• Determination of the minimum plasma concentration at steady state of fulvestrant when administered in combination with AZD2014. [ Time Frame: Samples will be obtained on Day 29 and Day 57 of multiple dosing ] [ Designated as safety issue: No ]
• Determination of the single dose PK profile of AZD2014,by assessments including: maximum plasma concentration (Cmax),time to Cmax,terminal rate constant half life,area under the plasma concentration-time curve (AUC0-12 and AUC0-24). [ Time Frame: At multiple time-points on the day of single dosing. This will be up to 5 days prior to the start of multiple dosing. ] [ Designated as safety issue: No ]

• To determine the minimum plasma concentration at steady state of fulvestrant when administered in combination with AZD2014. [ Time Frame: Samples will be obtained on Day 29 and Day 57 of multiple dosing ] [ Designated as safety issue: No ]
• To determine the single dose PK profile of AZD2014,by assessments including: maximum plasma concentration (Cmax),time to Cmax,terminal rate constant half life,area under the plasma concentration-time curve (AUC0-12 and AUC0-24). [ Time Frame: At multiple time-points on the day of single dosing. This will be up to 5 days prior to the start of multiple dosing. ] [ Designated as safety issue: No ]

The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant.

A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination with Intramuscular (IM) Fulvestrant to Patients with Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer

• Drug: AZD2014
  Single dose followed by multiple dosing
• Drug: Fulvestrant
  IM monthly after loading dose
  Other Name: faslodex

Inclusion Criteria:

• Provision of signed and dated written informed consent prior to any study specific procedures, sampling analysis
• Aged at least 18
• Histological or cytological confirmation of an ER+ advanced metastatic breast cancer tumour that is eligible for treatment with fulvestrant
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have evidence of non-child-bearing potential.

Exclusion Criteria:

• Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites)
• Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study.
• Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions.
• Patients with diabetes type 1 or uncontrolled type II (HbA1c > 8% assessed locally)