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