A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer

NCT ID: NCT04214288

Last Updated: 2025-11-20

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-22

Study Completion Date

2026-03-17

Brief Summary

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This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.

Detailed Description

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Post-menopausal women with histologically or cytologically confirmed metastatic or loco-regionally recurrent ER-positive HER2-negative breast cancer before randomization and fulfilling all of the inclusion criteria and none of the exclusion criteria will be included.

After the screening visit and confirmation of eligibility, patients will be randomly assigned in a 1:1:1:1 ratio to receive 1 of the following 4 treatments, consisting of 4-week treatment cycles until disease progression (assessed by the Investigator as defined by Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1):

* AZD9833 (Dose A)
* AZD9833 (Dose B)
* AZD9833 (Dose C)
* Fulvestrant (500 mg) During the treatment period, patients will have scheduled visits until treatment discontinuation. After the end of treatment, patients will attend 2 safety follow-up visits (at the time of treatment discontinuation and 28 days later) and will continue to be followed for survival.

As of December 2020, the Sponsor stopped enrolment to Dose C.

Conditions

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Advanced ER-Positive HER2-Negative Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AZD9833 Dose A

The patients will receive AZD9833 (Dose A).

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

Dosage formulation: AZD9833 tablets will be administered orally.

AZD9833 Dose B

The patients will receive AZD9833 (Dose B).

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

Dosage formulation: AZD9833 tablets will be administered orally.

AZD9833 Dose C

The patients will receive AZD9833 (Dose C).

Group Type EXPERIMENTAL

AZD9833

Intervention Type DRUG

Dosage formulation: AZD9833 tablets will be administered orally.

Fulvestrant 500 mg

The patients will receive Fulvestrant (500 mg).

Group Type ACTIVE_COMPARATOR

Fulvestrant

Intervention Type DRUG

Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.

Interventions

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AZD9833

Dosage formulation: AZD9833 tablets will be administered orally.

Intervention Type DRUG

Fulvestrant

Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Post-menopausal female patients aged at least 18 years.
* Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of the breast.
* Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.
* Patients must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.
* Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.
* Prior endocrine therapy as follows:

1. Recurrence or progression on at least one line of endocrine therapy
2. No more than 1 line of endocrine therapy for advanced disease
3. No more than 1 line of chemotherapy for advanced disease
4. Prior treatment with CDK4/6 inhibitors is permitted
5. No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies
* Inclusion criterion for the paired tumour biopsy research subgroup:

Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.

Exclusion Criteria

Intervention with any of the following:

* Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
* Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.
* Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 and sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.
* Drugs that are known to prolong QT and have a known risk of torsades de pointes.
* The following cardiovascular criteria: QTcF \>470 ms, resting heart rate \<45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction \<50%.
* Radiotherapy with a limited field of radiation for palliation within 1 week of dosing, or to \> 30% of bone marrow or a wide field within 4 weeks of dosing.
* Major surgical procedure or significant traumatic injury.
* Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system metastatic disease.
* 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 or fulvestrant.
* Previous randomisation in the present study.
* Women of childbearing potential.
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

Locations

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Research Site

Birmingham, Alabama, United States

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Long Beach, California, United States

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Fort Myers, Florida, United States

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St. Petersburg, Florida, United States

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Lincoln, Nebraska, United States

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Canton, Ohio, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Eagle River, Wisconsin, United States

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Brasschaat, , Belgium

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Charleroi, , Belgium

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Ghent, , Belgium

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Haine-Saint-Paul, , Belgium

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Leuven, , Belgium

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Libramont-Chevigny, , Belgium

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Namur, , Belgium

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Paris, , France

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Vandœuvre-lès-Nancy, , France

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Batumi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

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Berlin, , Germany

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Düsseldorf, , Germany

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Essen, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Kecskemét, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Jerusalem, , Israel

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Jerusalem, , Israel

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Nahariya, , Israel

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Petah Tikva, , Israel

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Bologna, , Italy

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Catanzaro, , Italy

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Meldola, , Italy

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Messina, , Italy

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Milan, , Italy

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Milan, , Italy

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Monza, , Italy

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Napoli, , Italy

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Roma, , Italy

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Umbria, , Italy

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Bydgoszcz, , Poland

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Lodz, , Poland

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Piła, , Poland

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Rzeszów, , Poland

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Skorzewo, , Poland

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Warsaw, , Poland

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Almada, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Kazan', , Russia

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Krasnodar, , Russia

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Kursk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Pyatigorsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Volgograd, , Russia

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Goyang-si, , South Korea

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Incheon, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Seville, , Spain

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Zaragoza, , Spain

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Cherkasy, , Ukraine

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Chernivtsі, , Ukraine

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Kyiv, , Ukraine

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M. Kyiv, , Ukraine

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S. Khodosivka, , Ukraine

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Uzhhorod, , Ukraine

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Derby, , United Kingdom

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Leicester, , United Kingdom

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Countries

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United States Belgium Canada France Georgia Germany Hungary Israel Italy Poland Portugal Russia South Korea Spain Ukraine United Kingdom

References

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Oliveira M, Pominchuk D, Nowecki Z, Hamilton E, Kulyaba Y, Andabekov T, Hotko Y, Melkadze T, Nemsadze G, Neven P, Vladimirov V, Zamagni C, Denys H, Forget F, Horvath Z, Nesterova A, Ajimi M, Kirova B, Klinowska T, Lindemann JPO, Lissa D, Mathewson A, Morrow CJ, Traugottova Z, van Zyl R, Arkania E. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol. 2024 Nov;25(11):1424-1439. doi: 10.1016/S1470-2045(24)00387-5.

Reference Type DERIVED
PMID: 39481395 (View on PubMed)

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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2023-504974-40-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-003706-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8530C00002

Identifier Type: -

Identifier Source: org_study_id

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