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Purpose

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent - Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing) - Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing - Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after >/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred >/=12 months since completion). - No prior systemic anti-cancer therapy for advanced disease - Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease - Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 - For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment

Exclusion Criteria

  • Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer - Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents - Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term - Active cardiac disease or history of cardiac dysfunction - Clinically significant history of liver disease

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Giredestrant + Investigator's Choice of CDK4/6i 		Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
  • Drug: Giredestrant
    Giredestrant 30 milligrams (mg) orally (PO) once a day (QD) on Days 1-28 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity.
    Other names:
    • RO7197597
    • RG6171
    • GDC-9545
  • Drug: Abemaciclib
    If chosen by the investigator as the CDK4/6i, participants will receive abemaciclib 150 mg PO twice per day (BID) on Days 1-28 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: Palbociclib
    If chosen by the investigator as the CDK4/6i, participants will receive palbociclib 125 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: Ribociclib
    If chosen by the investigator as the CDK4/6i, participants will receive ribociclib 600 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: LHRH Agonist
    Only pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each 28-day treatment cycle.
  • Diagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)
    F1LCDx is a next-generation sequencing (NGS)-based in vitro diagnostic test that detects and analyses genomic alterations in circulating cell-free DNA (cfDNA) isolated from plasma derived from the anti-coagulated peripheral whole blood of cancer patients. It will be used to determine the eligibility of participants requiring confirmation of ESR1 mutation status (mutation detected [ESR1m] vs. no mutation detected [ESR1nmd]).
    Other names:
    • F1LCDx
Active Comparator
Fulvestrant + Investigator's Choice of CDK4/6i 		Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
  • Drug: Fulvestrant
    Fulvestrant 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle until PD or unacceptable toxicity.
  • Drug: Abemaciclib
    If chosen by the investigator as the CDK4/6i, participants will receive abemaciclib 150 mg PO twice per day (BID) on Days 1-28 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: Palbociclib
    If chosen by the investigator as the CDK4/6i, participants will receive palbociclib 125 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: Ribociclib
    If chosen by the investigator as the CDK4/6i, participants will receive ribociclib 600 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
  • Drug: LHRH Agonist
    Only pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each 28-day treatment cycle.
  • Diagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)
    F1LCDx is a next-generation sequencing (NGS)-based in vitro diagnostic test that detects and analyses genomic alterations in circulating cell-free DNA (cfDNA) isolated from plasma derived from the anti-coagulated peripheral whole blood of cancer patients. It will be used to determine the eligibility of participants requiring confirmation of ESR1 mutation status (mutation detected [ESR1m] vs. no mutation detected [ESR1nmd]).
    Other names:
    • F1LCDx

Recruiting Locations

Southern Cancer Center
Daphne, Alabama 36526

La Hematology Oncology Medical Group
Glendale, California 91260

Marin Cancer Care Inc
Greenbrae, California 94904

Kaiser Permanente - Harbor City
Harbor City, California 90710

USC Norris Comprehensive Cancer Center
Los Angeles, California 90033

USC Norris Cancer Center
Newport Beach, California 92663

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente
Torrance, California 90502

Rocky Mountain Cancer Centers
Littleton, Colorado 80120-4413

Georgetown University Medical Center
Washington D.C., District of Columbia 20007

MedStar Washington Hosp Center
Washington D.C., District of Columbia 20010

AdventHealth Altamonte
Altamonte Springs, Florida 32701

Florida Cancer Specialists - Broadway
Fort Myers, Florida 33901

Cancer Specialists of North Florida
Jacksonville, Florida 32256

Florida Cancer Specialists - North;725 6th Ave South (St. Petersburg)
St. Petersburg, Florida 33701-4553

Comprehensive Hematology Oncology
St. Petersburg, Florida 33709

Florida Cancer Specialists - EAST - SCRI - PPDS
West Palm Beach, Florida 33401-3406

Grady Health System
Atlanta, Georgia 30303

Winship Cancer Institute of Emory University
Atlanta, Georgia 30329

Advocate Lutheran General Hospital
Park Ridge, Illinois 60068

Springfield Clinic
Springfield, Illinois 62702

Mission Cancer + Blood - IMMC
Des Moines, Iowa 50309

Baptist Health Lexington
Lexington, Kentucky 40503

Baptist Health Hamburg
Lexington, Kentucky 40509

Baptist Health Louisville
Louisville, Kentucky 40207

New England Cancer Specialists
Scarborough, Maine 04074

Maryland Oncology Hematology
Annapolis, Maryland 21401

Dana Farber Cancer Institute
Boston, Massachusetts 02215

Henry Ford Hospital
Detroit, Michigan 48202

HCA Midwest Division
Kansas City, Missouri 64132

Cancer Care Center of O'Fallon
O'Fallon, Missouri 62269

Oncology Hematology West - Grand Island
Grand Island, Nebraska 68803

Oncology Hematology West - Legacy
Omaha, Nebraska 68130-2042

Astera Cancer Care East Brunswick
East Brunswick, New Jersey 08816

Queens Hospital Cancer Center
Jamaica, New York 11432

Duke Women Cancer Care
Raleigh, North Carolina 27607

Asante Rogue Regional Medical Center
Medford, Oregon 97504-8332

Alliance Cancer Specialists
Bensalem, Pennsylvania 19020

Ann B. Barshinger Cancer Institute
Lancaster, Pennsylvania 17604

Abramson Cancer Center; Univ of Pennsylvania; Clinical Research Unit
Philadelphia, Pennsylvania 19106

Brown University Health
Providence, Rhode Island 02905

Medical University of South Carolina
Charleston, South Carolina 29425

Avera Cancer Institute - Aberdeen
Aberdeen, South Dakota 57401

Avera Cancer Institute
Sioux Falls, South Dakota 57105

West Cancer Center
Germantown, Tennessee 38138

SCRI Oncology Partners
Nashville, Tennessee 37203

Texas Oncology Cancer Center
Austin, Texas 78731

JPS Oncology & Infusion Center
Fort Worth, Texas 76104

Texas Oncology - DFW
Irving, Texas 75063

Virginia Cancer Specialists, PC
Fairfax, Virginia 22031

Virginia Commonwealth University - Massey Cancer Center
Richmond, Virginia 23219

Northwest Medical Specialties
Tacoma, Washington 98405

West Virginia University Hospitals Inc
Morgantown, West Virginia 26056

Aurora BayCare Medical Center
Green Bay, Wisconsin 54311

Aurora St Lukes Medical Center
Milwaukee, Wisconsin 53215

PanOncology Trials
San Juan, Puerto Rico 00935

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: CO44657 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.