Overview

A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer

Status:
Recruiting
Trial end date:
2023-01-23
Target enrollment:
0
Participant gender:
Female
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AstraZeneca
Treatments:
Fulvestrant
Criteria
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