A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease
SERENA-4
SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease
2 other identifiers
interventional
1,370
27 countries
263
Brief Summary
The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer. INFORMATION FOR TRIAL PARTICIPANTS In this trial, the researchers will look at how well camizestrant with palbociclib works, compared with anastrozole with palbociclib, in participants with breast cancer that has either spread into other parts of the body at the time of diagnosis, or has come back after at least 2 years of standard endocrine treatment. Participants in this trial will have breast cancer that has ER proteins but does not have overexpression of HER2 protein.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2021
Longer than P75 for phase_3
263 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 23, 2020
CompletedFirst Posted
Study publicly available on registry
January 15, 2021
CompletedStudy Start
First participant enrolled
January 28, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 24, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2029
October 14, 2025
October 1, 2025
5.6 years
December 23, 2020
October 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1
PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.
From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)
Secondary Outcomes (11)
Overall survival (OS)
From randomization until the date of death due to any cause (up to 8 years)
Second progression-free survival (PFS2)
From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)
Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1
From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (up to 5 years)
Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1
From the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)
Time to chemotherapy (TTC)
From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)
- +6 more secondary outcomes
Study Arms (2)
AZD9833 + palbociclib
EXPERIMENTALThe patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
Anastrozole + palbociclib
ACTIVE COMPARATORThe patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
Interventions
Dosage formulation: Anastrozole tablets will be administered orally.
Dosage formulation: anastrozole placebo tablets will be administrated orally.
Dosage formulation: AZD9833 placebo tablets will be administrated orally.
Dosage formulation: palbociclib tablets/capsules will be administered orally
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.
Eligibility Criteria
You may qualify if:
- Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with concomitant, approved LHRH agonists for the duration of the study treatment.
- De novo Stage 4 disease, or recurrence from early stage disease after at least 24 months of standard adjuvant endocrine therapy. Note that at least 12 months must have elapsed since the patient's last dose of adjuvant AI therapy without disease progression on treatment. Note that a 2-week washout period is required after the last dose of tamoxifen prior to randomisation.
- Histologically or cytologically documented diagnosis of ER+, HER2-negative breast cancer based on local laboratory results.
- Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease.
- Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic + sclerotic) bone lesion with a soft tissue component that can be assessed by CT or MRI.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Adequate organ and marrow function.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- INFORMATION FOR TRIAL PARTICIPANTS
- Participants can join the trial if they:
- Have breast cancer that cannot be treated with surgery or radiation
- Have breast cancer that has already spread into other parts of the body at the time of diagnosis, or has come back after at least 2 years of a standard endocrine treatment
- Have ER proteins but not overexpression of HER2 protein in their tumors
- Have never received any type of cancer therapy that affects the whole body for advanced breast cancer
- Are able to do their daily activities
You may not qualify if:
- Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor with disease recurrence while on or within 12 months of completing treatment.
- Prior exposure to AZD9833, other investigational SERDs/endocrine agents or fulvestrant.
- Participation in another clinical study with a study treatment or investigational medicinal device administered in the last 4 weeks prior to randomization or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term and/or impending visceral crisis
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
- Any clinically important and symptomatic heart disease .
- Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
- As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, renal transplant and active bleeding diseases) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
- Any concurrent anti-cancer treatment.
- Active infection including tuberculosis, HBV and HCV.
- INFORMATION FOR TRIAL PARTICIPANTS
- Participants cannot join the trial if they:
- Have uncontrolled cancer that has spread to the brain or the spinal cord
- Have received certain treatments for cancer in the past but the cancer came back within 1 year
- Had certain types of tumors in the past, which the study doctors think could come back
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (263)
Research Site
Mobile, Alabama, 36604, United States
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Springdale, Arkansas, 72762, United States
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Harbor City, California, 90710, United States
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Solvang, California, 93463, United States
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Lone Tree, Colorado, 80124, United States
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Fort Myers, Florida, 33901-8101, United States
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Jacksonville, Florida, 32256, United States
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West Palm Beach, Florida, 33401, United States
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Indianapolis, Indiana, 46256, United States
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Baton Rouge, Louisiana, 70809, United States
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Silver Spring, Maryland, 20904, United States
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Boston, Massachusetts, 02114, United States
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Detroit, Michigan, 48202, United States
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Hattiesburg, Mississippi, 39401, United States
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Omaha, Nebraska, 68130, United States
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Cincinnati, Ohio, 45219, United States
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Cincinnati, Ohio, 45267, United States
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Portland, Oregon, 97239, United States
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West Columbia, South Carolina, 29169, United States
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Sioux Falls, South Dakota, 57105, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Austin, Texas, 78731, United States
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Houston, Texas, 77030, United States
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Houston, Texas, 77090, United States
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Tyler, Texas, 75702, United States
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Fairfax, Virginia, 22031, United States
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Kennewick, Washington, 99336, United States
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Renton, Washington, 98055, United States
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Morgantown, West Virginia, 26505, United States
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Feldkirch, 6807, Austria
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Salzburg, 5020, Austria
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Vienna, 1130, Austria
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Anderlecht, 1070, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Namur, 5000, Belgium
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Sint-Niklaas, 9100, Belgium
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Plovdiv, 4000, Bulgaria
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Plovdiv, 4109, Bulgaria
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Shumen, 9700, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, V5Z 1H7, Canada
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Kitchener, Ontario, N2G 1G3, Canada
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London, Ontario, N6A 5W9, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, H3T 1E2, Canada
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Concepción, 4070196, Chile
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La Serena, 1720430, Chile
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Santiago, 7630370, Chile
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Santiago, 8241479, Chile
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Baoding, 071000, China
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Beijing, 100039, China
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Beijing, 100142, China
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Beijing, China
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Bengbu, 233060, China
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Changchun, 130000, China
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Changchun, 130021, China
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Changsha, 410013, China
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Chengdu, 610042, China
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Chongqing, 400042, China
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Dalian, 116011, China
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Guangzhou, 510060, China
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Guangzhou, 510100, China
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Guiyang, 550004, China
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Haikou, 570311, China
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Hangzhou, 310020, China
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Hangzhou, 310022, China
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Hefei, 230031, China
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Jinan, 250117, China
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Lanzhou, 730000, China
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Linyi, 276000, China
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Nanchang, 330009, China
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Nanjing, 210008, China
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Shanghai, 200025, China
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Shanghai, 200032, China
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Shenyang, 110001, China
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Tianjin, 300060, China
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Wuhan, 430000, China
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Wuhan, 430022, China
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Xi'an, 710061, China
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Zhengzhou, 450008, China
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Hořovice, 268 01, Czechia
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Hradec Králové, 500 05, Czechia
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Nový Jičín, 741 01, Czechia
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Prague, 100 34, Czechia
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Prague, 140 00, Czechia
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Prague, 150 06, Czechia
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Besançon, 25030, France
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Bordeaux, 33030, France
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Brest, 29609, France
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Caen, 14076, France
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Dijon, 21079, France
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Le Mans, 72000, France
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Lille, 59000, France
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Montpellier, 34070, France
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Pierre-Bénite, 69495, France
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Plerin SUR MER, 22190, France
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Saint-Cloud, 92210, France
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Vandœuvre-lès-Nancy, 54000, France
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Villejuif, 94805, France
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Berlin, 13125, Germany
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Dessau-RoBlau, 06847, Germany
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Essen, 45136, Germany
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Freiburg im Breisgau, 79110, Germany
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Mönchengladbach, 41061, Germany
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München, 81675, Germany
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Münster, 48145, Germany
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Regensburg, 93053, Germany
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Velbert, 42551, Germany
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Budapest, 1062, Hungary
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Budapest, 1088, Hungary
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Budapest, 1122, Hungary
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Győr, 9024, Hungary
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Miskolc, 3526, Hungary
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Nyíregyháza, 4400, Hungary
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Szekszárd, 7100, Hungary
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Zalaegerszeg, 8900, Hungary
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Ahmedabad, 380060, India
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Calicut, 673601, India
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Delhi, 110085, India
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Faridabad, 121001, India
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Gūrgaon, 122001, India
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Karamsad, 388325, India
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Kolkata, 700160, India
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Madurai, 625107, India
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Nagpur, 440001, India
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Nashik, 422009, India
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Nashik, 422011, India
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New Delhi, 11029, India
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Bergamo, 24127, Italy
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Florence, 50139, Italy
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Milan, 20141, Italy
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Modena, 41124, Italy
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Napoli, 80131, Italy
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Novara, 28100, Italy
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Padua, 35128, Italy
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Parma, 43100, Italy
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Prato, 59100, Italy
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Roma, 00168, Italy
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Roma, 161, Italy
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Rozzano, 20089, Italy
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Chūōku, 862-8655, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Isehara-shi, 259-1193, Japan
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Kitaadachi-gun, 362-0806, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-8556, Japan
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Kurashiki Shi, 701 0192, Japan
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Kurume-shi, 830-0013, Japan
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Kyoto, 606-8507, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 467-8602, Japan
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Nishinomiya-shi, 663-8501, Japan
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Osaka, 540-0006, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 003-0804, Japan
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Sendai, 980-8574, Japan
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Shimotsuke-shi, 329-0498, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 162-8655, Japan
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Suita-shi, 565-0871, Japan
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Takasaki-shi, 370-0829, Japan
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Tsu, 514-8507, Japan
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Tsukuba, 305-8576, Japan
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Yokohama, 241-8515, Japan
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George Town, 10450, Malaysia
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Johor Bahru, 81100, Malaysia
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Kuala Lumpur, 50586, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Kuala Selangor, 62250, Malaysia
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Kuching, 93586, Malaysia
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Del. Cuauhtemoc, 06700, Mexico
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Estado de México, 50080, Mexico
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La Paz, 23040, Mexico
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Mexico City, 0 3100, Mexico
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Monterrey, 64710, Mexico
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Puebla City, 72424, Mexico
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Drammen, 3004, Norway
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Oslo, N-0379, Norway
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Gdynia, 81-519, Poland
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Konin, 62-500, Poland
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Koszalin, 75-581, Poland
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Lodz, 90-302, Poland
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Lublin, 20-090, Poland
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Olsztyn, 10-513, Poland
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Poznan, 60-192, Poland
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Braga, 4710, Portugal
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Guimarães, 4835-044, Portugal
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Lisbon, 1400-038, Portugal
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Lisbon, 1500-650, Portugal
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Lisbon, 1998-018, Portugal
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Loures, 2674-514, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-319, Portugal
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Vila Nova de Gaia, 4434-502, Portugal
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Kaluga, 248007, Russia
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Kislino Village, Ryshkovsky Ru, 305524, Russia
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Moscow, 111123, Russia
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Moscow, 115478, Russia
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Moscow, 117997, Russia
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Moscow, 121467, Russia
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Saint Petersburg, 190103, Russia
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Saint Petersburg, 195067, Russia
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Saint Petersburg, 196603, Russia
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Saint Petersburg, 197758, Russia
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Banská Bystrica, 974 01, Slovakia
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Bratislava, 81250, Slovakia
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Bratislava, 833 01, Slovakia
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Prešov, 081 81, Slovakia
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Trenčín, 91171, Slovakia
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Busan, 49201, South Korea
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Daegu, 41404, South Korea
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Goyang-si, 10408, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Barcelona, 08908, Spain
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Barcelona, 8035, Spain
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Jaén, 23007, Spain
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Lleida, 25198, Spain
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Madrid, 28040, Spain
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Madrid, 28046, Spain
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Málaga, 29010, Spain
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Pamplona, 31008, Spain
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Santander, 39008, Spain
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Seville, 41013, Spain
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Valencia, 46015, Spain
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Liestal, CH- 4410, Switzerland
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Zurich, 8008, Switzerland
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Kaohsiung City, 82445, Taiwan
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Kaohsiung City, Taiwan
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Taichung, 40443, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 10048, Taiwan
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Taipei, 104, Taiwan
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Taipei, 110, Taiwan
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Taipei, 235, Taiwan
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Taoyuan District, 333, Taiwan
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Adana, 01120, Turkey (Türkiye)
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Ankara, 06010, Turkey (Türkiye)
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Ankara, 06230, Turkey (Türkiye)
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Ankara, 06340, Turkey (Türkiye)
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Ankara, 6100, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Izmir, 35620, Turkey (Türkiye)
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Kayseri, 38039, Turkey (Türkiye)
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Cambridge, CB2 2QQ, United Kingdom
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Colchester, CO4 5JL, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Surrey, GU2 7XX, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 23, 2020
First Posted
January 15, 2021
Study Start
January 28, 2021
Primary Completion (Estimated)
August 24, 2026
Study Completion (Estimated)
February 1, 2029
Last Updated
October 14, 2025
Record last verified: 2025-10
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 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.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.