A Comparative Study of AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer

• Status: Active, not recruiting
• Trial end date: 2022-12-28
• Target enrollment: 0
• Participant gender: Female

Summary

This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Fulvestrant

Criteria

Inclusion Criteria:

• Post-menopausal female patients aged at least 18 years.

• Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of the breast.

• Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.

• Patients must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.

• Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.

• Prior endocrine therapy as follows:

1. Recurrence or progression on at least one line of endocrine therapy

2. No more than 1 line of endocrine therapy for advanced disease

3. No more than 1 line of chemotherapy for advanced disease

4. Prior treatment with CDK4/6 inhibitors is permitted

5. No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies

• Inclusion criterion for the paired tumour biopsy research subgroup:

Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.

Exclusion Criteria:

Intervention with any of the following:

• Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.

• Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.

• Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 and sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.

• Drugs that are known to prolong QT and have a known risk of torsades de pointes.

• The following cardiovascular criteria: QTcF >470 ms, resting heart rate <45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction <50%.

• Radiotherapy with a limited field of radiation for palliation within 1 week of dosing, or to > 30% of bone marrow or a wide field within 4 weeks of dosing.

• Major surgical procedure or significant traumatic injury.

• Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system metastatic disease.

• 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.

• Previous randomisation in the present study.

• Women of childbearing potential.