This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the
biological effects, safety, tolerability, and pharmacokinetics (PK) of different doses of
oral AZD9833 in post-menopausal (and potentially pre-menopausal)women with primary breast
cancer.
The study will be conducted in approximately 20 study centers across 3 countries and will be
conducted in two stages (stage 1 and stage 2). After the screening visit and confirmation of
eligibility, evaluable participants will be enrolled across treatment groups. In stage 1, up
to 24 evaluable participants across two treatment groups will be enrolled. A Safety and Data
Monitoring Committee will convene to review stage 1 data and decide whether further treatment
groups are required in stage 2. Stage 2 may include up to 60 evaluable participants across up
to 5 treatment groups.
Stage 1 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily
Stage 2 (Optional) Group 1: AZD9833 Dose C once daily Group 2: AZD9833 Dose D once daily
Group 3: AZD9833 Dose E once daily Group 4: Fulvestrant 500 mg Group 5: AZD9833 Dose F once
daily (pre-menopausal women)
AZD9833 doses C, D, E or F could be the same as Dose A or Dose B from stage 1.
Adverse events and concomitant medications information will be collected throughout the
study. Thereafter there will be 28-day follow-up visit after discontinuation of study
treatment.
Inclusion criteria:
- Provision of written informed consent prior to study entry
- Female participants aged at least 18 years
- Post-menopausal status defined as meeting at least one of the following criteria:
1. Have undergone a bilateral oophorectomy
2. Age ≥ 60 years
3. Age ≥ 50 and < 60 years and with cessation of menses ≥ 12 months and
follicle-stimulating hormone and oestradiol levels in the post-menopausal range
and with an intact uterus in the absence of oral contraception or hormone
replacement therapy prior to the diagnosis of breast cancer
- Pre-menopausal status (Stage 2 only) defined as participants who are naturally
pre-menopausal (i.e. without concurrent ovarian suppression)
(a) Women of childbearing potential must: (i) Not be breastfeeding (ii) Have a
negative pregnancy test prior to the start of dosing (iii) Agree to use one highly
effective barrier method of contraception from the time of screening until 4 weeks
after discontinuing study treatment
- Female participants with newly diagnosed primary breast cancer scheduled to undergo
treatment with curative intent by surgery and irrespective of clinical node status
- Histologically confirmed invasive breast cancer involving a palpable tumour of any
size, or a tumour with an ultrasound assessed diameter of ≥ 1.0 cm
- Participants with adequately treated non-melanoma skin cancer, curatively treated
in-situ cancer of the cervix, or other solid tumours curatively treated with no
evidence of disease for ≥ 3 months can be considered for the study
- According to the local laboratory participants must have:
1. ER positive breast cancer
2. HER2-negative breast cancer
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Exclusion Criteria:
- Previous systemic or local treatment for the new primary breast cancer currently under
investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- Intervention with any of the following:
1. Use of sex-hormone-containing drugs within 6 months prior to the first dose of
study treatment
2. Medications or herbal supplements known to be strong inhibitors/inducers of
CYP3A4/5, sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9
and/or CYP2C19 which have a narrow therapeutic index
3. Drugs that are known to prolong QT and have a known risk of torsades de pointes
- Inflammatory breast cancer
- Any evidence of severe or uncontrolled systemic diseases which in the investigator's
opinion makes it undesirable for the participant to participate in the study
- Any of the following cardiovascular criteria: Mean resting QTcF > 470 msec; resting
heart rate of < 50 bpm; any clinically important abnormalities in rhythm, conduction,
or morphology of resting ECG; any factors that increase the risk of QTc prolongation
or risk of arrhythmic events; known left ventricular ejection fraction < 50%;
significant cardiovascular procedure or event within the last 6 months; uncontrolled
hypertension or symptomatic hypotension
- Inadequate bone marrow reserve or organ function
- Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases,
inability to swallow the formulated product, or previous significant bowel resection
that would preclude adequate absorption of AZD9833
- History of hypersensitivity to active or inactive excipients of AZD9833, or
fulvestrant (stage 2 only)
- Previous randomisation in the present study
- Judgement by the Investigator that the participant should not participate in the study
if the participant is unlikely to comply with study procedures, restrictions and
requirements
