UAMS - Translational Research Institute

A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)

Purpose

This Phase III, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus everolimus compared with the physician's choice of endocrine therapy plus everolimus in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) and endocrine therapy, either in the locally advanced/metastatic or the adjuvant setting.

Condition

Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent 2. Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally 3. Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing 4. Prior endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibitors in either setting as follows: - Metastatic setting: Disease progression after ≥6 months on ET plus CDK4/6 inhibitor in the locally advanced or metastatic setting. If ET plus CDK4/6 inhibitor is not the most recent therapy, then patient must also have had disease progression after ≥4 months on most recent ET - Adjuvant Setting: Relapse either while taking or within 12 months of exposure to combination adjuvant ET and CDK4/6 inhibitor. Patients must have taken at least 12 months of adjuvant ET, 6 months of which was in combination with a CDK4/6 inhibitor. 5. Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases. Patients with evaluable bone disease in the absence of measurable disease outside of the bone must have at least one predominantly lytic bone lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) which can be followed 6. Eastern Cooperative Oncology Group Performance Status 0-1 7. For women who are premenopausal or perimenopausal and for men: treatment with approved luteinizing hormone-releasing hormone (LHRH) agonist therapy for the duration of the study treatment

Exclusion Criteria

Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), novel oral selective estrogen receptor modulator (SERM), or everolimus in any setting. Prior fulvestrant is allowed if treatment was terminated at least 28 days prior to randomization. Prior treatment with tamoxifen is allowed. 2. Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting 3. Prior chemotherapy for locally advanced unresectable or metastatic disease 4. Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization 5. Treatment with any investigational therapy within 28 days prior to initiation of study treatment 6. Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization 7. History of any other malignancy other than breast cancer within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I endometrial cancer, or other non-breast cancers at very low risk of recurrence 8. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term 9. Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease 10. Active cardiac disease or history of cardiac dysfunction 11. Known clinically significant history of liver disease consistent with Child-Pugh Class B or C including active viral or other hepatitis virus, current alcohol abuse, or cirrhosis 12. Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection 13. Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy 14. Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization 15. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study 16. Known allergy or hypersensitivity to any of the study drugs or any of their excipients 17. For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists 18. Pregnant or breastfeeding

Study Design

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

Arm Groups

Arm	Description	Assigned Intervention
Experimental Giredestrant plus Everolimus		Drug: Giredestrant Participants will receive treatment with giredestrant 30 milligrams (mg) orally once a day (QD) on Days 1-28 of each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Other names: GDC-9545 RO7197597 RG6171 Drug: Everolimus Participants will receive treatment with everolimus 10 mg orally QD during each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Drug: LHRH Agonist Only premenopausal/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer. Drug: Dexamethasone Mouth Rinse A compounded alcohol-free mouthwash of dexamethasone (0.5 mg in 5 mL) will be supplied, where feasible. It is strongly recommended for prophylaxis or treatment of stomatitis/mucositis. Participants should use the alcohol-free mouthwash of dexamethasone four times QD for 8 weeks started concurrently with study treatment, and use it reactively thereafter with the first appearance of symptoms.
Active Comparator Physician's Choice of Endocrine Therapy plus Everolimus	The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen.	Drug: Exemestane If exemestane is chosen as the physician's choice of endocrine therapy, the participant will receive exemestane at a dose of 25 mg orally once a day (QD) on Days 1-28 of each 28-day cycle or as per local label, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1. Drug: Fulvestrant If fulvestrant is chosen as the physician's choice of endocrine therapy, the participant will receive fulvestrant in the clinic at a dose of 500 mg intramuscularly on Day 1 and Day 15 of Cycle 1, then Day 1 of each cycle thereafter (1 cycle is 28 days) or as per local prescribing information, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1. Drug: Tamoxifen If tamoxifen is chosen as the physician's choice of endocrine therapy, the participant will receive tamoxifen at a dose of 20 mg orally QD on Days 1-28 of each 28-day cycle or as per local prescribing information, until unacceptable toxicity or disease progression as determined by investigator according to RECIST v1.1. Drug: Everolimus Participants will receive treatment with everolimus 10 mg orally QD during each 28-day cycle until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Drug: LHRH Agonist Only premenopausal/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer. Drug: Dexamethasone Mouth Rinse A compounded alcohol-free mouthwash of dexamethasone (0.5 mg in 5 mL) will be supplied, where feasible. It is strongly recommended for prophylaxis or treatment of stomatitis/mucositis. Participants should use the alcohol-free mouthwash of dexamethasone four times QD for 8 weeks started concurrently with study treatment, and use it reactively thereafter with the first appearance of symptoms.

Recruiting Locations

Alabama Oncology - Bruno Cancer Center
Birmingham, Alabama 35205

Gulf Health Hospitals, Inc. d/b/a Infirmary Cancer Care
Mobile, Alabama 36607

Alaska Oncology and Hematology
Anchorage, Alaska 99508

The Dignity Health Cancer Institute
Phoenix, Arizona 85004

Arizona Oncology Associates, PC-CASA
Tucson, Arizona 85711

Genesis Cancer Center
Hot Springs, Arkansas 71913

University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute
Little Rock, Arkansas 72205

Pacific Cancer Medical Center
Anaheim, California 92801

Alta Bates Summit Medical Center; Comprehensive Cancer Center
Berkeley, California 94704

Beverly Hills Cancer Center
Beverly Hills, California 90211

TOI Clinical Research
Cerritos, California 90703

Newport Beach UC Irvine Medical Center
Costa Mesa, California 92627

Women's Cancer Care
Fresno, California 93710

Scripps Health; Scripps Cancer Center
La Jolla, California 92037

Los Angeles Hematology Oncology Medical Group
Los Angeles, California 90017

University of California, Irvine Medical Center
Orange, California 92868

Emad Ibrahim, Md, Inc
Redlands, California 92373

Brian LeBerthon, Med Corp
West Covina, California 91790-3961

Yale Cancer Center; Medical Oncology
New Haven, Connecticut 06520

Eastern CT Hematology and Oncology Associates
Norwich, Connecticut 06360-2740

ASCLEPES Research Centers - Brooksville
Brooksville, Florida 34613

Broward Health Medical Center (BHMC) (Broward General Medical Center (BGMC))
Fort Lauderdale, Florida 33316

Mount Sinai Medical Center
Miami Beach, Florida 33140

Orlando Health Cancer Institute
Orlando, Florida 32806

Cancer Care Centers of Brevard
Rockledge, Florida 32955

Florida Cancer Specialists
West Palm Beach, Florida 33401

Piedmont Atlanta Hospital
Atlanta, Georgia 30309

Piedmont Fayette Hospital
Fayetteville, Georgia 30214

Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia 30060

Piedmont Newnan Hospital
Newnan, Georgia 30265

Summit Cancer Care PC
Savannah, Georgia 31405

Piedmont Henry Hospital
Stockbridge, Georgia 30281

St Luke?s Cancer Institute
Boise, Idaho 83712

Northwestern University; Robert H. Lurie Comp Can Ctr
Chicago, Illinois 60611

Southern Illinois University, School of Medicine, Simmons Cancer Institute
Springfield, Illinois 62702

Springfield Clinic; Department of Hematology and Oncology
Springfield, Illinois 62702

Duly Health and Care
Tinley Park, Illinois 60487

Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202

Des Moines Oncology Research Association
Des Moines, Iowa 50309

University of Kansas Cancer Center
Westwood, Kansas 66205

Pikeville Medical Center
Pikeville, Kentucky 41501

LSU Health Baton Rouge; North Clinic
Baton Rouge, Louisiana 70805

Our Lady of the Lake Physicians Group; Hematology/Oncology
Baton Rouge, Louisiana 70808

Woman's Hospital
Baton Rouge, Louisiana 70817

Pontchartrain Cancer Center
Covington, Louisiana 70433

Northern Light Cancer Center/Oncology Research
Brewer, Maine 04412

New England Cancer Specialists
Scarborough, Maine 04074

Anne Arundel Health System Research Institute
Annapolis, Maryland 21401

University of Maryland Greenebaum Cancer Center
Baltimore, Maryland 21201

Mercy Medical Center
Baltimore, Maryland 21202

TidalHealth Peninsula Regional; Richard A. Henson Research
Ocean Pines, Maryland 21811

Sinai Hospital of Baltimore Inc
Randallstown, Maryland 21133

TidalHealth Peninsula Regional
Salisbury, Maryland 21801

Sinai Hospital of Baltimore; Wiliam E. Kahlert Regional Cancer Center
Westminster, Maryland 21157

Dana Farber Cancer Institute
Boston, Massachusetts 02215

Dana Farber/Harvard Cancer Center (Foxborough)
Foxboro, Massachusetts 02035

Dana Farber/Harvard Cancer Center (Milford)
Milford, Massachusetts 01757

Dana Farber/Harvard Cancer Center (Weymouth)
Weymouth, Massachusetts 02190

Michigan Center of Medical Research
Farmington Hills, Michigan 48334

Metro-Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota 55416

Oncology Hematology West PC
Grand Island, Nebraska 68803

Nebraska Cancer Specialists; Oncology Hematology West, PC
Omaha, Nebraska 68130

Renown Regional Medical Center
Reno, Nevada 89502

Memorial Sloan Kettering - Basking Ridge; Pharmacy
Basking Ridge, New Jersey 07920

Summit Medical Group; MD Anderson Cancer Center
Florham Park, New Jersey 07932

Memorial Sloan Kettering - Monmouth
Middletown, New Jersey 07748

Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
Montvale, New Jersey 07645

San Juan Oncology Associates
Farmington, New Mexico 87401

Memorial Sloan Kettering
Commack, New York 11725

Memorial Sloan Kettering Cancer Center at Westchester
Harrison, New York 10604

Memorial Sloan Kettering Cancer Center; Drug Shipment
Long Island City, New York 11104

The Blavatnik Family ? Chelsea Medical Center at Mount Sinai
New York, New York 10011

Icahn School of Medicine at Mount Sinai; Department of Pharmacy
New York, New York 10029

Icahn School of Medicine at Mount Sinai
New York, New York 10029

Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
New York, New York 10065

Stony Brook University Medical Center
Stony Brook, New York 11794

Memorial Sloan Kettering Cancer Center at Nassau
Uniondale, New York 11553

The Gabrail Pharmacology Phase 1 Research Center LLC
Canton, Ohio 44718

SCRI Mark H. Zangmeister Center
Columbus, Ohio 43219

University of Oklahoma Health Sciences Center; Peggy and Charles Stephenson Oklahoma Cancer Center
Oklahoma City, Oklahoma 73104

Oklahoma Cancer Specialists and Research Institute
Tulsa, Oklahoma 74146

St Charles Medical Center Bend; ATTN: Research
Bend, Oregon 97701

Oncology Research Office
Harrisburg, Pennsylvania 17109

Abramson Cancer Center; Univ of Pennsylvania
Philadelphia, Pennsylvania 19104

UPMC Hillman Cancer Center - Magee-Women?s Hospital
Pittsburgh, Pennsylvania 15213

Abramson Cancer Center Chester County Hospital; Hematology, Medical Oncology
West Chester, Pennsylvania 19380

McGlinn Cancer Institute at Reading Hospital
West Reading, Pennsylvania 19611

Avera Cancer Institute
Sioux Falls, South Dakota 57105

West Cancer Center
Germantown, Tennessee 38138

Thompson Cancer Survival Center
Knoxville, Tennessee 37916-2305

Texas Oncology P.A - Beaumont
Beaumont, Texas 77702

Texas Oncology
Bedford, Texas 76022

Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas 75246

Texas Oncology-Denton South
Denton, Texas 76201

Texas Oncology, P.A. - El Paso; El Paso Cancer Treatment Center, West
El Paso, Texas 79915

Methodist Hospital Research Institute
Houston, Texas 77030

Millennium Research & Clinical Development
Houston, Texas 77090

Lumi Research
Kingwood, Texas 77339

Texas Oncology Central - South
McAllen, Texas 78503

USOR - Texas Oncology - San Antonio Northeast
San Antonio, Texas 78217

Virginia Cancer Specialists
Fairfax, Virginia 22031

Inova Fairfax Hospital
Falls Church, Virginia 22031

Virginia Oncology Associates
Norfolk, Virginia 23502

Multicare Institute for Research and Innovation
Tacoma, Washington 98405

Northwest Medical Specialties, PLLC; Research Department
Tacoma, Washington 98405

UW Cancer Center at ProHealth
Waukesha, Wisconsin 53188

More Details

NCT ID: NCT05306340
Status: Recruiting
Sponsor: Genentech, Inc.

Study Contact

Reference Study ID Number: ML43171 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.