Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (SERENA-6)

A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study

The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation.

Study Overview

• Status: Recruiting
• Conditions: ER-Positive HER2-Negative Breast Cancer
• Intervention / Treatment: Drug: AZD9833; Drug: Anastrozole placebo; Drug: Palbociclib; Drug: Luteinizing hormone-releasing hormone (LHRH) agonist; Drug: Letrozole placebo; Drug: Abemaciclib; Drug: AZD9833 Placebo; Drug: Anastrozole; Drug: Letrozole; Drug: Ribociclib

Detailed Description

Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer.

This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well.

The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene.

Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:

• palbociclib + anastrozole
• palbociclib + letrozole
• abemaciclib + anastrozole
• abemaciclib + letrozole
• ribociclib + anastrozole
• ribociclib + letrozole

During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial.

In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative.

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

The researchers also want to know more about how safe AZD9833 is.

The trial participants will be split into 2 groups:

• Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo
• Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo

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 over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial.

Participants will visit their trial site regularly 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.

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

*Palbociclib and Abemacliclib cohorts are currently ongoing. Ribociclib cohort will be open pending on availability of the data.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Birtinya, Australia, 4575
    • Recruiting
    • Research Site
  • Darlinghurst, Australia, 2010
    • Recruiting
    • Research Site
  • Subiaco, Australia, 6008
    • Withdrawn
    • Research Site
• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Research Site
  • Innsbruck, Austria, 6020
    • Recruiting
    • Research Site
  • Salzburg, Austria, 5020
    • Recruiting
    • Research Site
  • Wien, Austria, 1090
    • Recruiting
    • Research Site
  • Wien, Austria, 1130
    • Recruiting
    • Research Site
• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Research Site
  • Liège, Belgium, 4000
    • Recruiting
    • Research Site
  • Namur, Belgium, 5000
    • Recruiting
    • Research Site
• Bulgaria
  • Haskovo, Bulgaria, 6300
    • Recruiting
    • Research Site
  • Panagyurishte, Bulgaria, 4500
    • Recruiting
    • Research Site
  • Pleven, Bulgaria, 5804
    • Recruiting
    • Research Site
  • Plovdiv, Bulgaria, 4004
    • Recruiting
    • Research Site
  • Plovdiv, Bulgaria, 4109
    • Withdrawn
    • Research Site
  • Sofia, Bulgaria, 1407
    • Recruiting
    • Research Site
  • Sofia, Bulgaria, 1431
    • Recruiting
    • Research Site
  • Sofia, Bulgaria, 1527
    • Recruiting
    • Research Site
  • Sofia, Bulgaria, 1303
    • Recruiting
    • Research Site
  • Sofia, Bulgaria, 1330
    • Recruiting
    • Research Site
  • Sofia, Bulgaria
    • Withdrawn
    • Research Site
• Canada
  • Ottawa, Canada, K1H 8L6
    • Recruiting
    • Research Site
  • Quebec, Canada, G1S 4L8
    • Recruiting
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • Research Site
  • Quebec
    • Levis, Quebec, Canada, G6V 3Z1
      • Recruiting
      • Research Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • Research Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Research Site
    • Montreal, Quebec, Canada, H2X 0C1
      • Recruiting
      • Research Site
• France
  • Avignon Cedex 09, France, 84918
    • Recruiting
    • Research Site
  • Brest, France, 29200
    • Recruiting
    • Research Site
  • Clermont-Ferrand, France, 63050
    • Recruiting
    • Research Site
  • Dijon, France, 21079
    • Recruiting
    • Research Site
  • Limoges, France, 83000
    • Recruiting
    • Research Site
  • Lorient cedex, France, 56322
    • Recruiting
    • Research Site
  • Lyon Cedex 08, France, 69373
    • Recruiting
    • Research Site
  • Marseille, France, 13273
    • Recruiting
    • Research Site
  • Metz-Tessy, France, 74370
    • Recruiting
    • Research Site
  • Nimes, France, 30029
    • Recruiting
    • Research Site
  • Paris Cedex 5, France, 75248
    • Recruiting
    • Research Site
  • Rouen, France, 76021
    • Recruiting
    • Research Site
  • Saint Herblain Cedex, France, 44805
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  • Saint-cloud, France, 92210
    • Recruiting
    • Research Site
  • Toulouse, France, 31100
    • Recruiting
    • Research Site
  • Tours, France, 37000
    • Recruiting
    • Research Site
  • Vandoeuvre les Nancy, France, 54519
    • Recruiting
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  • Vantoux, France, 57070
    • Recruiting
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  • Villejuif Cedex, France, 94805
    • Recruiting
    • Research Site
• Germany
  • Ansbach, Germany, 91522
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  • Aschaffenburg, Germany, 63739
    • Recruiting
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  • Augsburg, Germany, 86156
    • Recruiting
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  • Bonn, Germany, 53111
    • Recruiting
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  • Chemnitz, Germany, 09116
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    • Research Site
  • Dresden, Germany, 01307
    • Recruiting
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  • Erlangen, Germany, 91054
    • Recruiting
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  • Essen, Germany, 45130
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  • Mannheim, Germany, 68167
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    • Research Site
  • Ratingen, Germany, 40878
    • Recruiting
    • Research Site
  • Ravensburg, Germany, 88212
    • Recruiting
    • Research Site
  • Regensburg, Germany, 93053
    • Recruiting
    • Research Site
  • Stade, Germany, 21680
    • Recruiting
    • Research Site
  • Tübingen, Germany, 72076
    • Recruiting
    • Research Site
  • Ulm, Germany, 89075
    • Recruiting
    • Research Site
• Hungary
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    • Recruiting
    • Research Site
  • Budapest, Hungary, 1062
    • Recruiting
    • Research Site
  • Miskolc, Hungary, 3526
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    • Recruiting
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  • Szolnok, Hungary, 5000
    • Recruiting
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Recruiting
    • Research Site
• Israel
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    • Research Site
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    • Research Site
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    • Research Site
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    • Research Site
  • Ramat Gan, Israel, 5262000
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    • Research Site
• Italy
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    • Recruiting
    • Research Site
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    • Recruiting
    • Research Site
  • Firenze, Italy, 50134
    • Recruiting
    • Research Site
  • Meldola, Italy, 47014
    • Recruiting
    • Research Site
  • Milan, Italy, 20141
    • Recruiting
    • Research Site
  • Milano, Italy, 20132
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  • Misterbianco, Italy, 95045
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  • Napoli, Italy, 80131
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    • Research Site
  • Padova, Italy, 35128
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  • Rozzano, Italy, 20089
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• Japan
  • Chiba-shi, Japan, 260-8717
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  • Chuo-ku, Japan, 104-0045
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  • Hidaka-shi, Japan, 350-1298
    • Recruiting
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Recruiting
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  • Kitaadachi-gun, Japan, 362-0806
    • Recruiting
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  • Koto-ku, Japan, 135-8550
    • Recruiting
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  • Kumamoto-shi, Japan, 860-8556
    • Recruiting
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  • Matsuyama-shi, Japan, 791-0280
    • Recruiting
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  • Nagoya-shi, Japan, 464-8681
    • Recruiting
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  • Nagoya-shi, Japan, 467-8602
    • Recruiting
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  • Niigata-shi, Japan, 951-8566
    • Recruiting
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Recruiting
    • Research Site
  • Osaka-shi, Japan, 540-0006
    • Recruiting
    • Research Site
  • Ota-shi, Japan, 373-8550
    • Recruiting
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Recruiting
    • Research Site
  • Shinagawa-ku, Japan, 142-8666
    • Recruiting
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Recruiting
    • Research Site
  • Takasaki-shi, Japan, 370-0829
    • Recruiting
    • Research Site
  • Takatsuki-shi, Japan, 569-8686
    • Recruiting
    • Research Site
  • Tsukuba, Japan, 305-8577
    • Recruiting
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Recruiting
    • Research Site
• Korea, Republic of
  • Cheonan-si, Korea, Republic of, 31151
    • Recruiting
    • Research Site
  • Daegu, Korea, Republic of, 42415
    • Recruiting
    • Research Site
  • Goyang-si, Korea, Republic of, 10408
    • Recruiting
    • Research Site
  • Seongnam-Si, Korea, Republic of, 463-712
    • Recruiting
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06273
    • Recruiting
    • Research Site
• Norway
  • Drammen, Norway, 3004
    • Recruiting
    • Research Site
  • Oslo, Norway, 0450
    • Recruiting
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Recruiting
    • Research Site
  • Gdynia, Poland, 81-519
    • Recruiting
    • Research Site
  • Konin, Poland, 62-500
    • Withdrawn
    • Research Site
  • Koszalin, Poland, 75-581
    • Recruiting
    • Research Site
  • Lublin, Poland, 20-090
    • Withdrawn
    • Research Site
  • Olsztyn, Poland, 10-513
    • Withdrawn
    • Research Site
  • Poznan, Poland, 60-693
    • Recruiting
    • Research Site
  • Rzeszów, Poland, 35-001
    • Recruiting
    • Research Site
  • Tomaszów Mazowiecki, Poland, 97-200
    • Recruiting
    • Research Site
  • Warszawa, Poland, 02-781
    • Recruiting
    • Research Site
  • Łódź, Poland, 90-302
    • Recruiting
    • Research Site
• Portugal
  • Guimarães, Portugal, 4835-044
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1400-038
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1500-650
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1449-005
    • Recruiting
    • Research Site
  • Loures, Portugal, 2674-514
    • Recruiting
    • Research Site
  • Porto, Portugal, 4099-001
    • Recruiting
    • Research Site
  • Porto, Portugal, 4200-319
    • Recruiting
    • Research Site
  • Porto, Portugal, 4200-072
    • Recruiting
    • Research Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Recruiting
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 143423
    • Suspended
    • Research Site
  • Moscow, Russian Federation, 111123
    • Suspended
    • Research Site
  • Moscow, Russian Federation, 129090
    • Suspended
    • Research Site
  • Nizhny Novgorod, Russian Federation, 603126
    • Suspended
    • Research Site
  • Podolsk, Russian Federation, 142100
    • Suspended
    • Research Site
  • Saint Petersburg, Russian Federation, 197758
    • Suspended
    • Research Site
  • Sankt-Peterburg, Russian Federation, 197758
    • Suspended
    • Research Site
  • St. Petersburg, Russian Federation, 194017
    • Suspended
    • Research Site
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Recruiting
    • Research Site
  • Bratislava, Slovakia, 833 01
    • Recruiting
    • Research Site
  • Kosice, Slovakia, 041 91
    • Recruiting
    • Research Site
  • Michalovce, Slovakia, 07101
    • Recruiting
    • Research Site
  • Partizanske, Slovakia, 958 01
    • Recruiting
    • Research Site
• Spain
  • Badalona, Spain, 08003
    • Recruiting
    • Research Site
  • Barcelona, Spain, 8035
    • Recruiting
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08908
    • Recruiting
    • Research Site
  • La Coruna, Spain, 15006
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
  • Madrid, Spain, 28041
    • Recruiting
    • Research Site
  • Murcia, Spain, 30008
    • Recruiting
    • Research Site
  • Málaga, Spain, 29010
    • Recruiting
    • Research Site
  • Sant Joan Despi, Spain, 08970
    • Recruiting
    • Research Site
  • Sevilla, Spain, 41013
    • Recruiting
    • Research Site
  • Valencia, Spain, 46010
    • Recruiting
    • Research Site
• Switzerland
  • Bern, Switzerland, CH-3010
    • Recruiting
    • Research Site
  • Chur, Switzerland, CH-7000
    • Recruiting
    • Research Site
  • Winterthur, Switzerland, 8401
    • Recruiting
    • Research Site
• Taiwan
  • Kaohsiung city, Taiwan, 833
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40705
    • Recruiting
    • Research Site
  • Tainan, Taiwan, 70403
    • Recruiting
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  • Tainan, Taiwan, 710
    • Recruiting
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  • Taipei, Taiwan, 100
    • Recruiting
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  • Taipei, Taiwan, 11490
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    • Research Site
  • Taipei, Taiwan, 11259
    • Recruiting
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  • Taipei, Taiwan, 23561
    • Recruiting
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  • Taipei 112, Taiwan
    • Recruiting
    • Research Site
  • Taipei City, Taiwan, 110
    • Recruiting
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  • Taoyuan, Taiwan, 333
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• Turkey
  • Adana, Turkey, 01120
    • Recruiting
    • Research Site
  • Ankara, Turkey, 06340
    • Recruiting
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  • Ankara, Turkey, 06010
    • Recruiting
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  • Ankara, Turkey, 06520
    • Recruiting
    • Research Site
  • Ankara, Turkey, 06100
    • Terminated
    • Research Site
  • Izmir, Turkey, 35100
    • Recruiting
    • Research Site
  • Izmir, Turkey, 35360
    • Recruiting
    • Research Site
  • Kadıkoy/Istanbul, Turkey, 34722
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  • Karsiyaka, Turkey, 35575
    • Recruiting
    • Research Site
  • Kayseri, Turkey, 38039
    • Recruiting
    • Research Site
  • İstanbul, Turkey, 34457
    • Withdrawn
    • Research Site
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Research Site
  • Guildford, United Kingdom
    • Withdrawn
    • Research Site
  • Liverpool, United Kingdom, L7 3EW
    • Withdrawn
    • Research Site
  • London, United Kingdom, SW3 6JJ
    • Recruiting
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  • London, United Kingdom, WC1N 3BG
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  • Manchester, United Kingdom, M20 4BX
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  • Newport, United Kingdom, NP10 8FZ
    • Terminated
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  • Nottingham, United Kingdom, NG5 1PB
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  • Portsmouth, United Kingdom, PO6 3LY
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  • Reading, United Kingdom, RG2 9LH
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  • Sheffield, United Kingdom, S10 2SJ
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  • Sutton, United Kingdom, SM2 5PT
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• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
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  • Arkansas
    • Hot Springs National Park, Arkansas, United States, 71913
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    • Little Rock, Arkansas, United States, 72205
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  • California
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    • San Diego, California, United States, 92123
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    • Santa Rosa, California, United States, 92805
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    • Stanford, California, United States, 94305-5824
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  • Colorado
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    • Grand Junction, Colorado, United States, 81501
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    • Lone Tree, Colorado, United States, 80124
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  • Florida
    • Fort Lauderdale, Florida, United States, 33308
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    • Jacksonville, Florida, United States, 32256
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    • Atlanta, Georgia, United States, 30318
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    • Atlanta, Georgia, United States, 30342
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  • Illinois
    • Chicago, Illinois, United States, 60657
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      • Research Site
    • Oak Lawn, Illinois, United States, 60453
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    • Park Ridge, Illinois, United States, 60068
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    • Park Ridge, Illinois, United States, 60068
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  • Indiana
    • Fort Wayne, Indiana, United States, 46804
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    • Indianapolis, Indiana, United States, 46250
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  • Maryland
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      • Recruiting
      • Research Site
    • Ridgewood, New Jersey, United States, 07450
      • Recruiting
      • Research Site
  • New York
    • Bronx, New York, United States, 10469
      • Not yet recruiting
      • Research Site
    • Brooklyn, New York, United States, 11215
      • Recruiting
      • Research Site
    • East Syracuse, New York, United States, 13057
      • Recruiting
      • Research Site
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Research Site
    • New York, New York, United States, 10065
      • Recruiting
      • Research Site
    • New York, New York, United States, 10028
      • Not yet recruiting
      • Research Site
    • New York, New York, United States, 11355
      • Recruiting
      • Research Site
    • Shirley, New York, United States, 11967
      • Recruiting
      • Research Site
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Recruiting
      • Research Site
  • Ohio
    • Blue Ash, Ohio, United States, 45242
      • Recruiting
      • Research Site
    • Canton, Ohio, United States, 44710
      • Recruiting
      • Research Site
    • Cincinnati, Ohio, United States, 45220
      • Recruiting
      • Research Site
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Research Site
    • York, Pennsylvania, United States, 17403
      • Recruiting
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Recruiting
      • Research Site
    • West Columbia, South Carolina, United States, 29169
      • Recruiting
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Recruiting
      • Research Site
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Research Site
  • Texas
    • Bedford, Texas, United States, 76022
      • Recruiting
      • Research Site
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Research Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Research Site
    • Houston, Texas, United States, 77024
      • Recruiting
      • Research Site
    • Irving, Texas, United States, 75063
      • Recruiting
      • Research Site
    • Longview, Texas, United States, 75601
      • Recruiting
      • Research Site
    • Lubbock, Texas, United States, 79410
      • Recruiting
      • Research Site
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Recruiting
      • Research Site
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Recruiting
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Research Site
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53226
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they:

• Have advanced breast cancer that is not able to be treated with surgery or radiation;
• Have an ESR1 mutation in their cancer;
• Have breast cancer that is HR-positive and HER2-negative;
• Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking these drugs for at least 6 months;
• Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor;
• Are able to do their daily activities;
• Are at least 18.

Full list of inclusion criteria:

• Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent;
• Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results;
• Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) ± LHRH as the initial endocrine based treatment for advanced disease;
• Eastern Cooperative Oncology Group performance status of 0 or 1;
• ESR1m detected by central testing of ctDNA;
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Adequate organ and marrow function.

EXCLUSION CRITERIA:

INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they:

• Had certain types of tumors in the past that may come back;
• Are currently taking any other treatments for their cancer or other conditions including hormone replacements, medications, or supplements that could interfere with the trial treatment;
• Have or have had any major health problem, infection, or recent surgery that could make it difficult or dangerous to participate in this trial.

Full list of exclusion criteria:

• Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term;
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease;
• 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 or that would jeopardize compliance with the protocol;
• Patient with known or family history of severe heart disease;
• Previous treatment with AZD9833, investigational SERDs or fulvestrant;
• Currently pregnant (confirmed with positive pregnancy test) or breastfeeding;
• Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor and/or AI treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD9833 + palbociclib, abemaciclib or ribociclib; The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily)	Drug: AZD9833; Dosage formulation: AZD9833 tablets will be administered orally; Drug: Anastrozole placebo; Dosage formulation: anastrozole placebo tablets will be administrated orally.; Drug: Palbociclib; Dosage formulation: palbociclib tablets/capsules will be administered orally; Drug: Luteinizing hormone-releasing hormone (LHRH) agonist; Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.; Drug: Letrozole placebo; Dosage formulation: letrozole placebo tablets will be administered orally.; Drug: Abemaciclib; Dosage formulation: abemaciclib tablets will be administered orally; Drug: Ribociclib; Dosage formulation: ribociclib tablets will be administered orally
Active Comparator: Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib; The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)	Drug: Palbociclib; Dosage formulation: palbociclib tablets/capsules will be administered orally; Drug: Luteinizing hormone-releasing hormone (LHRH) agonist; Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.; Drug: Abemaciclib; Dosage formulation: abemaciclib tablets will be administered orally; Drug: AZD9833 Placebo; Dosage formulation: AZD9833 placebo tablets will be administrated orally.; Drug: Anastrozole; Dosage formulation: anastrozole tablets will be administered orally.; Drug: Letrozole; Dosage formulation: letrozole tablets will be administered orally.; Drug: Ribociclib; Dosage formulation: ribociclib tablets will be administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 1.1) or death.	From randomization until the earlier of the progression event or death (approximately 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival 2 (PFS2)	PFS2 is defined as the time from the 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 (approximately 3.5 years)
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 (approximately 5 years)
Chemotherapy free survival	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 (approximately 5 years)
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 complete response (CR) or partial response (PR), 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 (approximately 5 years)
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 randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)	At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment)
Change from baseline in EORTC QLQ-C30 scale scores	Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.	From baseline until second progression (approximately 5 years)
Change from baseline in EORTC QLQ-BR23 scale scores	Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.	From baseline until second progression (approximately 5 years)
Plasma concentration of AZD9833 at specified timepoints	To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib 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 for each patient

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): November 26, 2027

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasms; Double-Blind; Phase III; Metastatic; Ribociclib; Antineoplastic Agents; Breast Neoplasms; Physiological Effects of Drugs; Randomised; Endocrine Therapy; Letrozole; Palbociclib; Neoplasms by Site; Breast Diseases; Abemaciclib; Anastrozole; Multicentre; AZD9833; Next Generation Oral SERD; Antagonists; Estrogen Receptor Antagonists; Hormone Antagonists; camizestrant; ESR1m; Switch Treatment; Endocrine Resistance
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Palbociclib; Hormones; Anastrozole; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: D8534C00001; 2023-503990-39-00 (Other Identifier: EU CT number); 2021-000546-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No