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

NCT04588298 | Completed Phase 2 Results

• 2 other identifiers: D8530C000032020-001079-33
• Study Type: interventional
• Target: 135
• Locations: 3 countries
• Sites: 12

Brief 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 women with primary breast cancer

Conditions

HER2-negative Breast Cancer

Keywords

Breast cancer; Breast carcinoma; Estrogen-Receptor-positive breast cancer; HER2-negative breast cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Percentage Change From Baseline in Progesterone Receptor (PgR) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis)

  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)

  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)

  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)

  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)

  From screening (Day -21 to 1) through 28-day follow-up (Upto 2 months)

Study Arms (7)

Stage 1: AZD9833 Dose A

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.

Drug: AZD9833

Stage 1: AZD9833 Dose B

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.

Drug: AZD9833

Stage 2: AZD9833 Dose A

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study.

Drug: AZD9833

Stage 2: AZD9833 Dose B

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study.

Drug: AZD9833

Stage 2: AZD9833 Dose C

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.

Drug: AZD9833

Stage 3: AZD9833 Dose A

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study.

Drug: AZD9833

Stage 3: AZD9833: Dose B

EXPERIMENTAL

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 3 of the study.

Drug: AZD9833

Interventions

AZD9833 DRUG

AZD9833 tablets will be administered orally.

Stage 1: AZD9833 Dose A; Stage 1: AZD9833 Dose B; Stage 2: AZD9833 Dose A; Stage 2: AZD9833 Dose B; Stage 2: AZD9833 Dose C; Stage 3: AZD9833 Dose A; Stage 3: AZD9833: Dose B

Eligibility Criteria

• Age: 18 Years - 130 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Have undergone a bilateral oophorectomy
• Age ≥ 60 years
• 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:
• ER positive breast cancer
• HER2-negative breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

You may not qualify if:

• 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:
• Use of sex-hormone-containing drugs within 6 months prior to the first dose of study treatment
• 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
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (12)

Research Site

Batumi, 6000, Georgia

Location

Research Site

Tbilisi, '0112, Georgia

Location

Research Site

Tbilisi, '0186, Georgia

Location

Research Site

Tbilisi, 0159, Georgia

Location

Research Site

Tbilisi, 0179, Georgia

Location

Research Site

Aguascalientes, 20230, Mexico

Location

Research Site

Mexico City, '14080, Mexico

Location

Research Site

Derby, DE22 3NE, United Kingdom

Location

Research Site

Leicester, LE1 5WW, United Kingdom

Location

Research Site

Liverpool, L7 8XP, United Kingdom

Location

Research Site

London, W12 0HS, United Kingdom

Location

Research Site

Manchester, M23 9LT, United Kingdom

Location

Related Publications (1)

• Hamilton E, Oliveira M, Turner N, Garcia-Corbacho J, Hernando C, Ciruelos EM, Kabos P, Ruiz-Borrego M, Armstrong A, Patel MR, Vaklavas C, Twelves C, Boni V, Incorvati J, Brier T, Gibbons L, Klinowska T, Lindemann JPO, Morrow CJ, Sykes A, Baird RD. A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results. Ann Oncol. 2024 Aug;35(8):707-717. doi: 10.1016/j.annonc.2024.04.012. Epub 2024 May 8.

  PMID: 38729567 DERIVED

Related Links

• BreastCancerStudyLocator.com
• CSP\_Redacted
• SAP\_Redacted
• CSR Synopsis Redacted

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• John Robertson

  Graduate Entry Medicine & Health School, University of Nottingham, Royal Derby Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomised, open-label, parallel-group study. The study is divided into three stages as follows: 1. Stage 1: In this stage post-menopausal participants will be randomised in 2 cohorts in 1:1 ratio to receive AZD9833 with 12 evaluable participants in each cohort. 2. Stage 2: In this stage post-menopausal participants may be randomised in up to 3 cohorts, which may include up to 3 doses of AZD9833. 3. Stage 3 : In this stage post-menopausal participants may be randomised in up to 2 cohorts in 1:1 ratio, which may include up to 2 doses of AZD9833.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: October 19, 2020
• Study Start: November 2, 2020
• Primary Completion: June 19, 2023
• Study Completion: June 19, 2023
• Last Updated: January 24, 2025
• Results First Posted: January 24, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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

Locations

GB (5); GE (5); ME (2)