A Phase 2 interventional study of AZD9833 in HER2-negative Breast Cancer, sponsored by AstraZeneca. Completed at 12 sites in 3 countries. Open to female participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2025-01-24.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
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
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
12,815 studies on the registry are indexed under Breast Neoplasms; 2,920 are open to participants now.
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Post-menopausal status defined as meeting at least one of the following criteria:
According to the local laboratory participants must have:
Exclusion Criteria:
Intervention with any of the following:
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.
Drug: AZD9833
Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.
Drug: AZD9833
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study.
Drug: AZD9833
Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study.
Drug: AZD9833
Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.
Drug: AZD9833
Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study.
Drug: AZD9833
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.
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.
Time frame: 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.
Time frame: 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 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Days 5-7 or Days 12-15 (Pre and Post biopsy)
The study was conducted at 13 sites in 3 countries between November 2, 2020 and June 19, 2023.
| Milestone | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Started | 30 | 33 | 13 | 30 | 29 |
| Completed | 29 | 33 | 12 | 29 | 27 |
| Not completed | 1 | 0 | 1 | 1 | 2 |
| Withdrew: Adverse event | 0 | 0 | 1 | 0 | 2 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 1 | 0 |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in Estrogen Receptor (ER) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis) | -62.7 (-67.46 to -57.93) | -62.8 (-67.13 to -58.43) | -67.1 (-74.49 to -59.74) | -66.9 (-72.34 to -61.46) | -65.0 (-70.27 to -59.81) |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in ER Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis) | -62.1 (-67.00 to -57.25) | -62.3 (-66.64 to -57.88) | -66.6 (-74.00 to -59.14) | -66.9 (-72.34 to -61.46) | -65.0 (-70.27 to -59.81) |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in Progesterone Receptor (PgR) Expression Between Pre- and On-treatment Tumour Samples (Primary Analysis) | 194.8 (25.50 to 364.03) | -3.0 (-158.37 to 152.36) | 170.3 (-89.67 to 430.33) | -24.2 (-547.03 to 498.69) | 463.8 (-38.45 to 966.02) |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in PgR Expression Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis) | -35.2 (-45.86 to -24.57) | -44.0 (-53.09 to -34.90) | -36.7 (-52.96 to -20.52) | -61.8 (-76.93 to -46.62) | -55.0 (-71.29 to -38.78) |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Primary Analysis) | -40.3 (-52.78 to -24.49) | -79.4 (-83.37 to -74.55) | -78.2 (-84.82 to -68.77) | -73.0 (-79.42 to -64.64) | -77.5 (-82.68 to -70.86) |
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.
| Percentage change from baseline | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Percentage Change From Baseline in Ki-67 Labelling Index Between Pre- and On-treatment Tumour Samples (Sensitivity Analysis) | -49.3 (-62.18 to -31.96) | -81.3 (-85.14 to -76.49) | -78.9 (-85.37 to -69.46) | -81.7 (-86.45 to -75.24) | -81.9 (-86.38 to -75.88) |
The safety and tolerability of AZD9833 in this patient population was evaluated.
| Participants | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Any AE | 9 | 17 | 9 | 11 | 19 |
| Any AE possibly related to treatment | 4 | 14 | 6 | 10 | 17 |
| Any AE of CTCAE grade 3 or higher | 0 | 1 | 0 | 0 | 0 |
| Any AE of CTCAE grade 3 or higher, possibly related to treatment | 0 | 1 | 0 | 0 | 0 |
| Any AE with outcome = death | 0 | 0 | 0 | 0 | 0 |
| Any AE with outcome = death, possibly related to treatment | 0 | 0 | 0 | 0 | 0 |
| Any SAE (including events with outcome = death) | 0 | 0 | 0 | 0 | 0 |
| Any SAE (including events with outcome = death), possibly related to treatment | 0 | 0 | 0 | 0 | 0 |
| Any SAE leading to discontinuation of treatment | 0 | 0 | 0 | 0 | 0 |
| Any SAE leading to discontinuation of treatment, possibly related to treatment | 0 | 0 | 0 | 0 | 0 |
| Any AE leading to discontinuation of treatment | 0 | 0 | 1 | 0 | 2 |
| Any AE leading to discontinuation of treatment, possibly related to treatment | 0 | 0 | 0 | 0 | 2 |
| Any AE leading to dose modification of treatment | 0 | 0 | 0 | 0 | 0 |
| Any AE leading to dose modification of treatment, possibly related to treatment | 0 | 0 | 0 | 0 | 0 |
| Any other significant AEs | 0 | 0 | 0 | 0 | 0 |
The plasma concentration of AZD9833 in this participant population was evaluated
| Nanograms per milliliter | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Days 5-7 or Days 12-15 (Pre-biopsy) | 50.712 ± 74.1 | 122.134 ± 103.8 | 180.773 ± 173.3 | 46.939 ± 56.3 | 120.516 ± 70.0 |
| Days 5-7 or Days 12-15 (Post-biopsy) | 58.304 ± 62.2 | 142.916 ± 102.4 | 213.446 ± 175.6 | 54.075 ± 42.8 | 137.687 ± 55.4 |
Collected over From screening (Day -21 to 1) through 28-day follow-up (Up to 2 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AZD9833 75 mg (Stage 1 + 2) | 0/30 (0%) | 0/30 (0%) | 7/30 (23.3%) |
| AZD9833 150 mg (Stage 1 + 2) | 0/33 (0%) | 0/33 (0%) | 17/33 (51.5%) |
| AZD9833 300 mg (Stage 2) | 0/13 (0%) | 0/13 (0%) | 9/13 (69.2%) |
| AZD9833 75 mg (Stage 3) | 0/30 (0%) | 0/30 (0%) | 11/30 (36.7%) |
| AZD9833 150 mg (Stage 3) | 0/29 (0%) | 0/29 (0%) | 19/29 (65.5%) |
| Event | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) |
|---|---|---|---|---|---|
| Visual impairmentEye disorders | 0/30 | 5/33 | 3/13 | 6/30 | 7/29 |
| HypertensionVascular disorders | 1/30 | 2/33 | 3/13 | 1/30 | 4/29 |
| DiplopiaEye disorders | 0/30 | 4/33 | 1/13 | 0/30 | 5/29 |
| PhotopsiaEye disorders | 2/30 | 4/33 | 2/13 | 3/30 | 4/29 |
| NauseaGastrointestinal disorders | 4/30 | 3/33 | 1/13 | 2/30 | 1/29 |
| HeadacheNervous system disorders | 2/30 | 3/33 | 1/13 | 3/30 | 3/29 |
| DizzinessNervous system disorders | 0/30 | 2/33 | 1/13 | 2/30 | 3/29 |
| Sinus bradycardiaCardiac disorders | 0/30 | 0/33 | 0/13 | 0/30 | 3/29 |
| FatigueGeneral disorders | 2/30 | 3/33 | 0/13 | 0/30 | 0/29 |
| COVID-19Infections and infestations | 0/30 | 0/33 | 1/13 | 0/30 | 0/29 |
Safety Analysis Set was defined as all patients who received any amount of study treatment, regardless of whether that was the randomized therapy intended.
| Age, Continuous(Years) | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) | Total |
|---|---|---|---|---|---|---|
| Mean | 62.0 ± 7.35 | 65.7 ± 7.53 | 66.3 ± 8.20 | 64.0 ± 8.65 | 67.2 ± 10.03 | 64.9 ± 8.49 |
| Sex: Female, Male(Participants) | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) | Total |
|---|---|---|---|---|---|---|
| Female | 30 | 33 | 13 | 30 | 29 | 135 |
| Male | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 30 | 33 | 13 | 30 | 29 | 135 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | AZD9833 75 mg (Stage 1 + 2) | AZD9833 150 mg (Stage 1 + 2) | AZD9833 300 mg (Stage 2) | AZD9833 75 mg (Stage 3) | AZD9833 150 mg (Stage 3) | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 4 | 5 | 9 |
| Not Hispanic or Latino | 29 | 32 | 13 | 26 | 24 | 124 |
| Other | 1 | 1 | 0 | 0 | 0 | 2 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — 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
Supporting information: Study protocol, Statistical analysis plan
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
Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com
Ran from Nov 2020 to primary completion in Jun 2023, 31 months.
Results were first posted in Jan 2025, 1 year 7 months after primary completion.
Of 218 industry-sponsored phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 55. This study's 31 months is below that.
Counting every sponsor, half of 1,201 studies reached it within 49 months; a quarter within 31 and three quarters within 80.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: AZD9833