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

ER-Positive HER2-Negative Breast Cancer Clinical Trial

— SERENA-4  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04711252
• Other study ID #: D8532C00001
• Secondary ID: 2020-002276-12
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 28, 2021
• Est. completion date: February 1, 2029

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

A Randomised, Multicentre, Double-Blind, Phase III study will evaluate the safety and efficacy of AZD9833 (next generation oral SERD) in combination with palbociclib versus anastrozole in combination with palbociclib for the treatment of patients with ER-positive breast cancer. The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

INFORMATION FOR TRIAL PARTICIPANTS

Researchers are looking for a better way to treat breast cancer.

In people with cancer, some cells have grown out of control to form tumours.

The trial drugs palbociclib, camizestrant, and anastrozole are designed to work by blocking the cancer's ability to grow. Camizestrant is also called AZD9833. Palbociclib and anastrozole are already available as treatments for people with certain type of breast cancer.

In this trial, the researchers want to find out how well taking camizestrant with palbociclib, or anastrozole with palbociclib, works in participants with breast cancer that has ER proteins but does not have overexpression of HER2 protein.

The researchers will look at which trial treatments help the participants live longer with cancer before it gets worse.

The trial will split participants into 2 groups:

• Participants in Group 1 will take camizestrant, palbociclib, and a placebo matched with anastrazole.

• Participants in Group 2 will take anastrozole, palbociclib, , and a placebo matched with camizestrant.

A placebo looks like a treatment but does not have any medicine in it.

A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.

The participants will take their trial treatments in periods called "cycles". Each cycle will last 28 days. During each cycle, the participants will take:

• camizestrant or anastrozole once daily by mouth

• palbociclib once daily by mouth for 21 days. Then, they will not take any palbociclib for 7 days

Some participants will also get either goserelin or leuprorelin once every month. Participants could get goserelin or leuprorelin if:

• They are medically determined yet to reach menopause status

• They are male

They will get this treatment as an injection under the skin or into a muscle. Goserelin and leuprorelin work by decreasing the amount of sex hormones made by the body which will lead to reduction of ER production. This can help stop breast cancer from growing.

Participants will take trial treatment until the cancer gets worse or they leave the trial.

Participants will visit their trial site several times throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1370
• Est. completion date: February 1, 2029
• Est. primary completion date: August 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

INCLUSION CRITERIA

Full list of inclusion criteria

• 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

EXCLUSION CRITERIA

Full list of exclusion criteria

• 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

• Are currently taking any treatment for cancer or are taking medications or supplements that affect certain proteins in the body

• Have any major health problem, infection, or surgery that could make it difficult or dangerous to participate in this trial, such as tuberculosis, HIV, heart problems, or a kidney transplant

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Breast Neoplasms
• ER-Positive HER2-Negative Breast Cancer

Intervention

Drug:
• AZD9833
Dosage formulation: AZD9833 tablets will be administered orally
• Anastrozole
Dosage formulation: Anastrozole tablets will be administered orally.
• Anastrozole placebo
Dosage formulation: anastrozole placebo tablets will be administrated orally.
• AZD9833 placebo
Dosage formulation: AZD9833 placebo tablets will be administrated orally.
• Palbociclib
Dosage formulation: palbociclib tablets/capsules will be administered orally
• Luteinizing hormone-releasing hormone (LHRH) agonist
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Locations

Country	Name	City	State
Austria	Research Site	Feldkirch
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Anderlecht
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Namur
Belgium	Research Site	Sint-Niklaas
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Shumen
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Chile	Research Site	Concepcion
Chile	Research Site	La Serena
Chile	Research Site	Santiago
Chile	Research Site	Santiago
China	Research Site	Baoding
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Lanzhou
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Czechia	Research Site	Horovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Novy Jicin
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
France	Research Site	Besancon Cedex
France	Research Site	Bordeaux
France	Research Site	Brest Cedex
France	Research Site	Caen Cedex 05
France	Research Site	Dijon
France	Research Site	Le Mans
France	Research Site	Lille
France	Research Site	Montpellier
France	Research Site	Pierre Benite Cedex
France	Research Site	Plerin SUR MER
France	Research Site	Saint-cloud
France	Research Site	Vandoeuvre Les Nancy
France	Research Site	Villejuif Cedex
Germany	Research Site	Berlin
Germany	Research Site	Dessau-RoBlau
Germany	Research Site	Essen
Germany	Research Site	Freiburg
Germany	Research Site	Mönchengladbach
Germany	Research Site	München
Germany	Research Site	Münster
Germany	Research Site	Regensburg
Germany	Research Site	Velbert
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Szekszárd
Hungary	Research Site	Zalaegerszeg
India	Research Site	Ahmedabad
India	Research Site	Calicut
India	Research Site	Delhi
India	Research Site	Faridabad
India	Research Site	Gurgaon
India	Research Site	Karamsad
India	Research Site	Kolkata
India	Research Site	Madurai
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	Nashik
India	Research Site	New Delhi
Italy	Research Site	Bergamo
Italy	Research Site	Firenze
Italy	Research Site	Milan
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Novara
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Prato
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurashiki shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Ota-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shimotsuke-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Takasaki-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	George Town
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Mexico	Research Site	Del. Cuauhtemoc
Mexico	Research Site	Estado de México
Mexico	Research Site	La Paz
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Mexico	Research Site	Puebla
Norway	Research Site	Drammen
Norway	Research Site	Oslo
Poland	Research Site	Gdynia
Poland	Research Site	Konin
Poland	Research Site	Koszalin
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Portugal	Research Site	Braga
Portugal	Research Site	Guimarães
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Loures
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Vila Nova de Gaia
Russian Federation	Research Site	Kaluga
Russian Federation	Research Site	Kislino Village, Ryshkovsky Ru
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Sankt-Peterburg
Slovakia	Research Site	Banská Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Prešov
Slovakia	Research Site	Trencin
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Jaén
Spain	Research Site	Lleida
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Pamplona
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Switzerland	Research Site	Liestal
Switzerland	Research Site	Zürich
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
Turkey	Research Site	Kayseri
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Colchester
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Surrey
United States	Research Site	Austin	Texas
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Harbor City	California
United States	Research Site	Hattiesburg	Mississippi
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kennewick	Washington
United States	Research Site	Lone Tree	Colorado
United States	Research Site	Mobile	Alabama
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Nashville	Tennessee
United States	Research Site	Omaha	Nebraska
United States	Research Site	Portland	Oregon
United States	Research Site	Renton	Washington
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Solvang	California
United States	Research Site	Springdale	Arkansas
United States	Research Site	Tyler	Texas
United States	Research Site	West Columbia	South Carolina
United States	Research Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Norway,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival (OS)	The OS is defined as the time from randomization to death due to any cause.	From randomization until the date of death due to any cause (up to 8 years)
Secondary	Second progression-free survival (PFS2)	Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.	From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)
Secondary	Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1	ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 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)
Secondary	Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1	The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.	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)
Secondary	Time to chemotherapy (TTC)	Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.	From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)
Secondary	Time to first subsequent anti-cancer therapy (TFST)	TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.	From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years)
Secondary	Clinical benefit rate at 24 weeks (CBR24)	CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window).	At least 23 weeks after randomisation
Secondary	Time to second subsequent therapy (TSST)	TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.	From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years)
Secondary	Plasma concentration of AZD9833 at specified timepoints	To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.	on Day 15
Secondary	Change from baseline in EORTC QLQ-C30 scale scores	Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.	From baseline to 24 weeks post progression (up to approximately 5 years)
Secondary	Change from baseline in EORTC QLQ-BR45 scale scores	Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.	From baseline to 24 weeks post progression (up to approximately 5 years)

External Links

•   BreastCancerStudyLocator.com