A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer (SERENA-3)

A Randomised, Open-Label, Parallel-Group, Pre-surgical Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2-negative Primary Breast Cancer (SERENA-3)

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 women with primary breast cancer

Study Overview

• Status: Completed
• Conditions: HER2-negative Breast Cancer
• Intervention / Treatment: Drug: AZD9833

Detailed Description

The study will be conducted in approximately 20 study centers across 3 countries and will be conducted in three stages (stage 1, stage 2 and stage 3). 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 will include participants across up to 3 treatment groups. Stage 3 will include two treatment groups:

Stage 1 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily

Stage 2 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily Group 3: AZD9833 Dose C once daily

Stage 3 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily

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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Batumi, Georgia, 6000
    • Research Site
  • Tbilisi, Georgia, 0179
    • Research Site
  • Tbilisi, Georgia, '0112
    • Research Site
  • Tbilisi, Georgia, '0186
    • Research Site
  • Tbilisi, Georgia, 0159
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Mexico City, Mexico, '14080
    • Research Site
• United Kingdom
  • Derby, United Kingdom, DE22 3NE
    • Research Site
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • Liverpool, United Kingdom, L7 8XP
    • Research Site
  • London, United Kingdom, W12 0HS
    • Research Site
  • Manchester, United Kingdom, M23 9LT
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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 for stages 1 and 2 at screening;resting heart rate <60 bpm at screening for Stage 3; 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: AZD9833 Dose A; Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 1: AZD9833 Dose B; Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 2: AZD9833 Dose A; Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 2: AZD9833 Dose B; Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 2: AZD9833 Dose C; Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 3: AZD9833 Dose A; Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.
Experimental: Stage 3: AZD9833: Dose B; Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 3 of the study.	Drug: AZD9833; AZD9833 tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Estrogen Receptor (ER) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)	The pharmacodynamic (PD) effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by immunohistochemistry (IHC) method. The percentage change was calculated from an analysis of covariance (ANCVOA) model adjusting for baseline ER score and day of on-treatment biopsy.	Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
Percentage Change From Baseline in ER Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)	The PD effect of AZD9833 on ER expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline ER H-score < 10. The percentage change was calculated from ANCVOA model adjusting for baseline ER score and day of on-treatment biopsy.	Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Progesterone Receptor (PgR) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)	The PD effects of AZD9833 on PgR expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The percentage change was calculated from an ANCOVA model adjusting for baseline PgR score and day of on-treatment biopsy.	Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
Percentage Change From Baseline in PgR Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)	The PD effects of AZD9833 on PgR expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline PgR H-score < 10. The percentage change was calculated from an ANCOVA model adjusting for baseline PgR score and day of on-treatment biopsy.	Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Primary Analysis)	The PD effect of AZD9833 on antigen Ki-67 expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The percentage change was calculated from an ANCOVA model adjusting for log baseline Ki67 index and day of on-treatment biopsy. The Ki-67 index data were log transformed prior to analysis, with results back-transformed to represent percentage change.	Baseline (Screening Day -21 to 1) to Biopsy day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis)	The PD effect of AZD9833 on antigen Ki-67 expression comparing pre- and on-treatment tumour samples in women with early breast cancer after 5 to 7 days and 12 to 15 days of AZD9833 treatment was assessed. The assessment was done by IHC method. The sensitivity analysis excluded any patients who were HER2-positive patient by central assessment as well as patients with baseline Ki67 labelling index <5%. The percentage change was calculated from an ANCOVA model adjusting for log baseline Ki67 index and day of on-treatment biopsy. The Ki-67 index data were log transformed prior to analysis, with results back-transformed to represent percentage change.	Baseline (Screening Day -21 to 1) to Biopsy Day (Days 5-7 [Stage 1 and 2] or Days 12-15 [Stage 3])
Number of Patients With Adverse Events (AEs)	The safety and tolerability of AZD9833 in this patient population was evaluated.	From screening (Day -21 to 1) through 28-day follow-up (Upto 2 months)
Plasma Concentrations of AZD9833	The plasma concentration of AZD9833 in this participant population was evaluated	Days 5-7 or Days 12-15 (Pre and Post biopsy)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: John Robertson, Graduate Entry Medicine & Health School, University of Nottingham, Royal Derby Hospital

Publications and helpful links

Helpful Links

• BreastCancerStudyLocator.com
• CSP_Redacted
• SAP_Redacted
• CSR Synopsis Redacted

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): June 19, 2023
• Study Completion (Actual): June 19, 2023

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; HER2-negative breast cancer; Breast carcinoma; Estrogen-Receptor-positive breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: D8530C00003; 2020-001079-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No