Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.
Condition: Postmenopausal Women With ER+ HER2- Primary Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open label randomised multicentre pre-surgical pharmacodynamics study to compare
      and assess the biological effects of AZD9496 and fulvestrant in postmenopausal women with
      estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor 2 (HER-2)
      negative (HER2-) primary breast cancer.

      Patients will receive AZD9496 or fulvestrant and will have an on-treatment image

      -guided core biopsy after 5-14 days of commencing treatment.
    

Detailed description: 
      This is an open label, randomized, multi-centre study in postmenopausal women with primary
      ER+ HER2- breast cancer. Patients will be randomised to an oral dose of 250 mg bd AZD9496 or
      500mg fulvestrant i.m. administered on one occasion. Patients diagnosed with primary breast
      cancer who are scheduled for surgery with curative intent will be consented to the study
      including consent to use the formalin fixed paraffin embedded (FFPE) diagnostic tumor biopsy
      sample and fresh frozen tumor biopsy sample (if available) for research purposes. Patients
      may also consent to provide an optional pretreatment fresh frozen tumor biopsy sample if this
      was not obtained at the time of initial diagnostic biopsy. If the diagnostic biopsy was taken
      ≥ 6 weeks prior to starting treatment or was not of sufficient quality, new tumor core
      biopsies (FFPE and fresh frozen) must be taken. Following the screening visit, eligible
      patients will be randomised to receive one of the following study treatments:

        -  AZD9496 administered at 250 mg bd orally for 5-14 days commencing on Day 1, and
           continuing up to the day of biopsy OR

        -  fulvestrant 500 mg administered as two consecutive 5 ml intramuscular injections on Day
           1, one in each buttock.

      After the morning dose of AZD9496 on the day of biopsy dosing will be stopped. If following
      initiation of AZD9496 treatment, dosing will be stopped if biopsy is postponed beyond Day 14.
      Patients will be considered not evaluable for the study if biopsy is postponed beyond day 14
      of AZD9496/fulvestrant treatment initiation. Core tumor biopsies will be taken at either the
      time of definitive surgery or at a separate visit prior to surgery in the period between (and
      including) day 5 and day 14. Subjects who are scheduled to start a subsequent neoadjuvant
      therapy must have their core tumor biopsies performed before commencing neoadjuvant
      treatment.
    

Intervention name(s): Standard Arm - Fulvestrant; AZD9496
Intervention type(s): Drug; Drug
Intervention description(s): 500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock; Administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy
Other intervention name(s): Fulvestrant; Study drug
Intervention MeSH terms: Fulvestrant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment