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

NCT04214288 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: D8530C000022023-504974-40-002019-003706-27
• Study Type: interventional
• Target: 240
• Locations: 16 countries
• Sites: 86

Brief Summary

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.

Conditions

Advanced ER-Positive HER2-Negative Breast Cancer

Keywords

Open-Label; Parallel-Group; Fulvestrant; ER-Positive HER2-Negative Breast Cancer; Metastatic; AZD9833; Oral SERD; Camizestrant

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

  From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  From screening until disease progression (up to data cut-off of 29 months)

• Duration of Response (DoR)

  From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)

• Percentage Change in Tumour Size at 16 Weeks

  At Week 16

• Overall Survival (OS)

  From the date of randomisation until death (up to data cut-off of 29 months)

• Clinical Benefit Rate at 24 Weeks (CBR24)

  At Week 24

Other Outcomes (1)

• Number of Patients With Adverse Events

  From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)

Study Arms (4)

AZD9833 Dose A

EXPERIMENTAL

The patients will receive AZD9833 (Dose A).

Drug: AZD9833

AZD9833 Dose B

EXPERIMENTAL

The patients will receive AZD9833 (Dose B).

Drug: AZD9833

AZD9833 Dose C

EXPERIMENTAL

The patients will receive AZD9833 (Dose C).

Drug: AZD9833

Fulvestrant 500 mg

ACTIVE COMPARATOR

The patients will receive Fulvestrant (500 mg).

Drug: Fulvestrant

Interventions

AZD9833 DRUG

Dosage formulation: AZD9833 tablets will be administered orally.

AZD9833 Dose A; AZD9833 Dose B; AZD9833 Dose C

Fulvestrant DRUG

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

Fulvestrant 500 mg

Eligibility Criteria

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

You may qualify if:

• 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:
• Recurrence or progression on at least one line of endocrine therapy
• No more than 1 line of endocrine therapy for advanced disease
• No more than 1 line of chemotherapy for advanced disease
• Prior treatment with CDK4/6 inhibitors is permitted
• No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies
• Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (86)

Research Site

Birmingham, Alabama, 35205, United States

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Long Beach, California, 90806, United States

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Fort Myers, Florida, 33901, United States

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St. Petersburg, Florida, 33705, United States

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Lincoln, Nebraska, 68506, United States

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Canton, Ohio, 44710, United States

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Chattanooga, Tennessee, 37404, United States

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Nashville, Tennessee, 37203, United States

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Eagle River, Wisconsin, 54521, United States

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Brasschaat, 2930, Belgium

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Charleroi, 6000, Belgium

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Ghent, 9000, Belgium

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Haine-Saint-Paul, 7100, Belgium

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Leuven, 3000, Belgium

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Libramont-Chevigny, 6800, Belgium

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Namur, 5000, Belgium

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Paris, 75005, France

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Vandœuvre-lès-Nancy, 54519, France

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Batumi, 6000, Georgia

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Tbilisi, '0112, Georgia

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Tbilisi, '0159, Georgia

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Tbilisi, '0186, Georgia

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Tbilisi, 0159, Georgia

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Tbilisi, 0186, Georgia

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Berlin, 10707, Germany

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Düsseldorf, 40225, Germany

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Essen, 45136, Germany

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Budapest, 1122, Hungary

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Debrecen, 4032, Hungary

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Kaposvár, 7400, Hungary

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Kecskemét, 6000, Hungary

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Nyíregyháza, 4400, Hungary

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Pécs, 7624, Hungary

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Szeged, 6725, Hungary

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Jerusalem, 91031, Israel

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Jerusalem, 9112001, Israel

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Nahariya, 22100, Israel

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Petah Tikva, 4941492, Israel

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Bologna, 40138, Italy

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Catanzaro, 88100, Italy

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Meldola, 47014, Italy

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Messina, 98158, Italy

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Milan, 20141, Italy

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Milan, 20121, Italy

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Monza, 20900, Italy

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Napoli, 80131, Italy

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Roma, 00128, Italy

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Umbria, 5100, Italy

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Bydgoszcz, 85-796, Poland

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Lodz, 93-513, Poland

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Piła, 64-920, Poland

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Rzeszów, 35-021, Poland

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Skorzewo, 60-185, Poland

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Warsaw, 02-781, Poland

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Almada, 2805-267, Portugal

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Lisbon, 1400-038, Portugal

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Lisbon, 1449-005, Portugal

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Lisbon, 1998-018, Portugal

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Kazan', 420029, Russia

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Krasnodar, 350040, Russia

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Kursk, 305035, Russia

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Moscow, 115478, Russia

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Moscow, 123056, Russia

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Pyatigorsk, 357502, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 197082, Russia

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Saint Petersburg, 197758, Russia

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Volgograd, 400138, Russia

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Goyang-si, 10408, South Korea

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Incheon, 405-760, South Korea

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Barcelona, 08035, Spain

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Barcelona, 08190, Spain

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Madrid, 28050, Spain

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Seville, 41013, Spain

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Zaragoza, 50009, Spain

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Cherkasy, 18009, Ukraine

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Chernivtsі, 58013, Ukraine

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Kyiv, 03039, Ukraine

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M. Kyiv, 02094, Ukraine

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S. Khodosivka, 08173, Ukraine

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Uzhhorod, 88000, Ukraine

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Derby, DE22 3NE, United Kingdom

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Leicester, LE1 5WW, United Kingdom

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Related Publications (2)

• 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.

  PMID: 39481395 DERIVED

• 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

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MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

AZD9833; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

At the time of CSR finalization, CSP version 5.0 was available, therefore, CSP version 5.0 was redacted and submitted along with the Results Registration Form. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

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

Study Record Dates

• First Submitted: December 27, 2019
• First Posted: January 2, 2020
• Study Start: April 22, 2020
• Primary Completion: August 30, 2022
• Study Completion: March 17, 2026
• Last Updated: November 20, 2025
• Results First Posted: December 12, 2023

Record last verified: 2025-11

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 refer 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 de-identified 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

US (9); BE (7); GB (2); GE (6); CA (3); ES (5); HU (7); RU (10); KR (2); UA (6); FR (2); PT (4); IT (10); IL (4); DE (3); PL (6)