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

NCT ID: NCT04588298

Last Updated: 2025-01-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-02

Study Completion Date

2023-06-19

Brief Summary

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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

Detailed Description

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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

Conditions

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HER2-negative Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stage 1: AZD9833 Dose A

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 1: AZD9833 Dose B

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 2: AZD9833 Dose A

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 2: AZD9833 Dose B

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 2: AZD9833 Dose C

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 3: AZD9833 Dose A

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Stage 3: AZD9833: Dose B

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

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

AZD9833 tablets will be administered orally.

Interventions

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AZD9833

AZD9833 tablets will be administered orally.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Robertson

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Research Site

Batumi, , Georgia

Site Status

Research Site

Tbilisi, , Georgia

Site Status

Research Site

Tbilisi, , Georgia

Site Status

Research Site

Tbilisi, , Georgia

Site Status

Research Site

Tbilisi, , Georgia

Site Status

Research Site

Aguascalientes, , Mexico

Site Status

Research Site

Mexico City, , Mexico

Site Status

Research Site

Derby, , United Kingdom

Site Status

Research Site

Leicester, , United Kingdom

Site Status

Research Site

Liverpool, , United Kingdom

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Countries

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Georgia Mexico United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38729567 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-001079-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8530C00003

Identifier Type: -

Identifier Source: org_study_id

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