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

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04588298

Collaborator

(none)

Enrollment

Locations

Arms

28.2

Anticipated Duration (Months)

4.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HER2-negative Breast Cancer	Drug: AZD9833	Phase 2

Detailed Description

The study will be conducted in approximately 20 study centers across 3 countries and will be conducted in two stages (stage 1 and stage 2). 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 may include participants across up to 3 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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomised, open-label, parallel-group study. The study is divided into two stages as follows: 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. Stage 2 (Optional): In this stage post-menopausal participants may be randomised in up to 3 cohorts, which may include up to 3 doses of AZD9833.This is a randomised, open-label, parallel-group study. The study is divided into two stages as follows: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. Stage 2 (Optional): In this stage post-menopausal participants may be randomised in up to 3 cohorts, which may include up to 3 doses of AZD9833.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Nov 2, 2020

Anticipated Primary Completion Date :

Mar 10, 2023

Anticipated Study Completion Date :

Mar 10, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Change from baseline in estrogen receptor (ER) expression between pre- and on-treatment tumour samples measured by immunohistochemistry (IHC) [Baseline (Screening Day -21 to 1) and Days 5 to 7]
To explore the ER pharmacodynamic (PD) effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 treatment.

Secondary Outcome Measures

Change from baseline in progesterone receptor (PgR) expression between pre- and on-treatment tumour samples measured by IHC [Baseline (Screening Day -21 to 1) and Days 5 to 7]
To explore the PgR PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833.
Change from baseline in Ki-67 labelling index between pre- and on-treatment tumour samples measured by IHC [Baseline (Screening Day -21 to 1) and Days 5 to 7]
To explore the Ki-67 PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833.
Number of adverse events (AEs) experienced by participants [From screening (Day -21 to 1) through 28-day follow-up (Upto 2 months)]
Safety and tolerability will be assessed through the incidence of AEs.
Plasma concentrations of AZD9833 on the biopsy day [Days 5 to 7]
To evaluate the PK of AZD9833 in this participant population.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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:

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

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:

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; 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Batumi	Georgia	6000
2	Research Site	Tbilisi	Georgia	'0112
3	Research Site	Tbilisi	Georgia	'0186
4	Research Site	Tbilisi	Georgia	0159
5	Research Site	Tbilisi	Georgia	0179
6	Research Site	Tbilisi	Georgia	0186
7	Research Site	Aguascalientes	Mexico	20230
8	Research Site	D.F	Mexico	14000
9	Research Site	Mexico City	Mexico	'14080
10	Research Site	México	Mexico	06726
11	Research Site	Tlalpan	Mexico	14050
12	Research Site	Bournemouth	United Kingdom	BH7 7DW
13	Research Site	Derby	United Kingdom	DE22 3NE
14	Research Site	Leicester	United Kingdom	LE1 5WW
15	Research Site	Liverpool	United Kingdom	L7 8XP
16	Research Site	London	United Kingdom	W12 0HS
17	Research Site	Manchester	United Kingdom	M23 9LT
18	Research Site	Poole	United Kingdom	BH15 2JB
19	Research Site	Sutton In Ashfield	United Kingdom	NG17 4JL