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RecruitingInterventionalPhase 3

A Phase IIIb Study to Characterize the Efficacy and Safety of Adjuvant Ribociclib Plus Endocrine Therapy in a Close-to-clinical Practice Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)

NCT ID: NCT05827081Sponsor: Novartis PharmaceuticalsLast updated: 2026-06-09

Summary

The purpose of this open-label, multicenter, phase IIIb, single-arm study is to characterize the efficacy and safety of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a close to clinical practice patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, IIB, and a subset of Stage IIA Early Breast Cancer (EBC).

Detailed description

The study consists of Screening, Treatment, and Follow-up periods. * Treatment Period: all participants who complete screening will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily ET for 36 months (approximately 39 cycles) from the date of first dose. The Treatment Period starts when the patient receives their first dose of ribociclib and ends at the time of the 30-day Safety Follow-up. All treated participants should have a Safety Follow-up call conducted 30 days after the last dose of study treatment. * Follow-up period: participants will be followed from 30 days after study treatment (i.e., ribociclib) completion/discontinuation (i.e. 30-day Safety Follow-up) until death, withdrawal of consent, lost to follow-up, or until 48 months after the last participant has received their first dose of study treatment (i.e. End of Study \[EOS\]), whichever occurs first.

Arms & interventions

  • DrugRibociclib

    Ribociclib 400 mg orally once daily on days 1-21 of a 28 day cycle followed by 7 days rest

  • DrugLetrozole

    Letrozole 2.5 mg orally once daily continuously

  • DrugAnsastrozole

    Anastrozole 1 mg orally once daily continuously.

  • DrugGoserelin

    Goserelin administered subcutaneously at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used

  • DrugLeuprolide

    Leuprolide administered subcutaneously at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used

  • DrugExemestane

    Exemestane 25 mg once daily continuously

Outcome measures

Primary

  • Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years

    iBCFS is defined as the time from the date of first dose to the date of the first event of invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), or contralateral invasive BC. iBCFS will be assessed using STEEP criteria version 2.0 (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator. The iBCFS rate at 3 years will be assessed.

    Time frame: At 3 years

Secondary

  • Incidence and severity of adverse events (AEs) using CTCAE v4.03

    Time frame: Up to approximately 6 years

  • Invasive Disease-Free Survival (iDFS)

    Time frame: Up to approximately 6 years

  • Distant Disease-Free Survival (DDFS)

    Time frame: Up to approximately 6 years

  • Distant Relapse-Free Survival (DRFS)

    Time frame: Up to approximately 6 years

  • Recurrence-Free Interval (RFI)

    Time frame: Up to approximately 6 years

  • Relative dose intensity (RDI) of ribociclib

    Time frame: Up to 3 years

  • Overall Survival (OS)

    Time frame: Up to approximately 6 years

  • Time To Discontinuation (TTD) of ribociclib

    Time frame: Up to 3 years

  • Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score

    Time frame: Up to approximately 6 years

  • Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score

    Time frame: Up to approximately 6 years

  • Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score

    Time frame: Up to approximately 6 years

  • Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score

    Time frame: Up to approximately 6 years

  • Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score

    Time frame: Up to approximately 6 years

Eligibility criteria

Sex: AllAge: 18 Years to 100 YearsHealthy volunteers: No
Key Inclusion criteria: * Participant is an adult, male or female ≥ 18 years of age at the time of informed consent form signature (IC). * Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC) based on the most recently analyzed tissue sample tested by a local laboratory prior to enrollment. * Participant has HER2- BC defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing based on the most recently analyzed tissue sample. * Participants may have already received any standard neoadjuvant and/or adjuvant ET, including tamoxifen or toremifene at the time of informed consent signature, but enrollment should occur within 36 months of prior ET start date and participants should have at least 3 years remaining of endocrine adjuvant therapy. * For participants with prior ET treatment \> 12 months, restaging is highly recommended (unless contradictory to local regulations) to rule out disease recurrence prior to enrollment. * The number of participants with prior ET between 12 and 36 months will be capped at 30%. The cap will not apply to Black or African American participants. * Participant has no contraindication to receive adjuvant ET in the study. * Participant after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories: * Anatomic Stage Group III, or * Anatomic Stage Group IIB, or * A subset of Anatomic Stage Group IIA. * Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2. * Participant has adequate bone marrow and organ function. * ECG values assessed by KardiaMobile-6L device, or standard 12-lead ECG per local investigator where KardiaMobile-6L cannot be used, as: * QTcF interval at Screening \< 450 msec (QT interval using Fridericia's correction). * Mean resting heart rate 50-99 beats per minute (determined from the ECG). Key Exclusion criteria: * Participant with distant metastases of BC beyond regional lymph nodes (Stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery. * Participant is concurrently using other antineoplastic therapy with the exception of adjuvant ET. * Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol, or limit life expectancy to ≤5 years. * Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. * Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial. * Women of child-bearing potential (CBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 21 days after stopping the treatment. Other inclusion/exclusion criteria may apply

Study locations (78)

Central Alabama Research

Birmingham, Alabama, 35209

Recruiting
Lorie Szymela · Contact
David Mooney · Principal Investigator

Alaska Oncology and Hematology LLC

Anchorage, Alaska, 99508

Recruiting
Talia Wyckoff · Contact
Steven Liu · Principal Investigator

Western Reg MC-COH Phoenix

Goodyear, Arizona, 85338

Recruiting
Susan Sheerin-Fadden · Contact
Cynthia Lynch · Principal Investigator

CARTI Cancer Center

Little Rock, Arkansas, 72205

Recruiting
Emily Johnson · Contact
Issam Sam Makhoul · Principal Investigator

Beverly Hills Cancer Center

Beverly Hills, California, 90211

Recruiting
Linnea Chap · Principal Investigator

Onco Inst of Hope and Innovation

Cerritos, California, 90703

Recruiting
Pamela Miel · Principal Investigator

City of Hope National Medical

Duarte, California, 91010

Recruiting
Felicia Lewis · Contact
Thanh Nga Doan · Principal Investigator

Providence Medical Foundation

Fullerton, California, 92835

Recruiting
Teresa Olea · Contact
Giribala R Patel · Principal Investigator

Palo Alto Medical Foundation

Mountain View, California, 94040

Recruiting
Natalia Colocci · Principal Investigator

UC Irvine Medical Center

Orange, California, 92868

Recruiting
Stephany Ruiz · Contact
Ritesh Parajuli · Principal Investigator

Sutter Inst Medical Research

Sacramento, California, 95816-5199

Recruiting
Nitin Rohatgi · Principal Investigator

School Of Medicine

Sacramento, California, 95817

Recruiting
Apinya Vorasaph · Contact
Mili Arora · Principal Investigator

Rocky Mountain Cancer Centers

Denver, Colorado, 80218

Recruiting
Mabel Mardones · Principal Investigator

Georgetown University Lombardi Cancer Center

Washington D.C., District of Columbia, 20007-2197

Recruiting
Katia Khoury · Principal Investigator

Washington Hospital Center

Washington D.C., District of Columbia, 20010

Recruiting
Ami Chitalia · Principal Investigator

AdventHealth Altamonte Springs

Altamonte Springs, Florida, 32701

Recruiting
Rebecca Iorio · Contact
Wassim Mchayleh · Principal Investigator

Holy Cross Health

Fort Lauderdale, Florida, 33308

Recruiting
Karim Arnaout · Principal Investigator

Hialeah Hospital

Hialeah, Florida, 33013

Recruiting
Jonathan Matias · Contact
Luis G Rangel · Principal Investigator

Memorial Cancer Institute

Hollywood, Florida, 33021

Recruiting
Florencia Brunengo · Contact
Adriana Milillo Naraine · Principal Investigator

Jupiter Medical Center

Jupiter, Florida, 33458

Recruiting
Danielle Krol · Principal Investigator

Ocala Research Institute, Inc

Ocala, Florida, 34474

Recruiting
Anju Vasudevan · Principal Investigator

University Cancer and Blood Center LLC

Athens, Georgia, 30607

Recruiting
Christen Nicole Cooper Pope · Contact
Amanda Hathaway · Principal Investigator

Summit Cancer Care PC

Savannah, Georgia, 31405

Recruiting
Theresa Williams · Contact
Mark A Taylor · Principal Investigator

Hawaii Cancer Care

Honolulu, Hawaii, 96813

Recruiting
Angelei Gommesen · Contact
Arnold K N Yee · Principal Investigator

Affiliated Oncologists IL

Chicago, Illinois, 60415

Recruiting
Angela Malone · Contact
Rami Haddad · Principal Investigator

Hope And Healing Care

Hinsdale, Illinois, 60521

Recruiting
Divya Mudavath · Contact
Srilata Gundala · Principal Investigator

Midwestern Reg MC COH Chicago

Zion, Illinois, 60099

Recruiting
Afua Amoabin · Contact
Ajaz Khan · Principal Investigator

Investigative Clinical R of Indiana

Indianapolis, Indiana, 46260

Recruiting
Zara Edgell · Contact
Ruemu Birhiray · Principal Investigator

University of Iowa Health Care

Waukee, Iowa, 50263

Recruiting
Theresa Caon · Contact
Seema Harichand-Herdt · Principal Investigator

University of Kansas Cancer Center

Westwood, Kansas, 66205

Recruiting
Chasity Cupp · Contact
Priyanka Sharma · Principal Investigator

Cancer Center of Kansas

Wichita, Kansas, 67214-3728

Recruiting
Shaker R Dakhil · Principal Investigator

Willis-Knighton Cancer Center

Shreveport, Louisiana, 71103

Recruiting
Briana Barrow · Contact
Prakash Peddi · Principal Investigator

Mercy Medical Center

Baltimore, Maryland, 21202

Recruiting
Alexandra Cline · Contact
David Andrew Riseberg · Principal Investigator

Maryland Oncology Hematology P A

Silver Spring, Maryland, 20904

Recruiting
Teresa Saavedra · Contact
Carol Tweed · Principal Investigator

Boston Medical Center

Boston, Massachusetts, 02118

Recruiting
Tara Hassani Goodarzi · Contact
Jose J Acevedo · Principal Investigator

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Erica Mayer · Principal Investigator

Dana Farber Brigham Women Cancer

Milford, Massachusetts, 01757

Recruiting
Natalie Sinclair · Principal Investigator

Minnesota Oncology Hematology P A

Minneapolis, Minnesota, 55404

Recruiting
Anne Rabenn · Contact
Eric Lander · Principal Investigator

Allina Hlth Cancer Inst Minneapolis

Minneapolis, Minnesota, 55407

Recruiting
Jonathan Alexander · Contact
Daniel Carlson · Principal Investigator

Jackson Oncology Associates

Jackson, Mississippi, 39202

Recruiting
Justin T Baker · Principal Investigator

HCA Midwest Division

Kansas City, Missouri, 64132

Recruiting
Katie Burnside · Contact
Anis Toumeh · Principal Investigator

WA Uni School Of Med

St Louis, Missouri, 63110

Recruiting
Elizabeth Ainsworth · Contact
Katherine Clifton · Principal Investigator

Intermountain Healthcare

Billings, Montana, 59102

Recruiting
Kelsi Margaris · Contact
Patrick Cobb · Principal Investigator

Nebraska Cancer Specialists

Omaha, Nebraska, 68154

Recruiting
Margaret Barbara Block · Principal Investigator

Renown Regional Medical Center

Reno, Nevada, 89502

Recruiting
Bayley Stoner · Contact
Lee Schwartzberg · Principal Investigator

Cancer Care Specialists

Reno, Nevada, 89511

Recruiting
Layla Quinonez · Contact
Sowjanya Reganti · Principal Investigator

Summit Health

Florham Park, New Jersey, 07932

Recruiting
Steven Papish · Principal Investigator

The Valley Hospital

Ridgewood, New Jersey, 07450

Recruiting
Emily Clark · Contact
Amanda Podolski · Principal Investigator

Presbyterian Medical Group

Albuquerque, New Mexico, 87110

Recruiting
Monique Robertson · Contact
Yashvin Onkarappa Mangala · Principal Investigator

Queens Cancer Center of Queens Hospital

Jamaica, New York, 11432

Recruiting
Linda Bulone · Contact
Ellen Hagopian · Principal Investigator

Optum Health

Lake Success, New York, 11042

Recruiting
Jonathan Goldberg · Principal Investigator

Mount Sinai School of Medicine

New York, New York, 10029

Recruiting
Weronika Bucwinska · Contact
Melanie Kier · Principal Investigator

Duke Cancer Network

Durham, North Carolina, 27710

Recruiting
Catrin Davies · Contact
Madhu Chaudhry · Principal Investigator

Cone Health Cancer Center

Greensboro, North Carolina, 27403

Recruiting
Vinay Gudena · Principal Investigator

Sanford Research USD Fargo

Fargo, North Dakota, 58122

Recruiting
Anu Goel Gaba · Principal Investigator

Good Samaritan Regional Medical Center

Corvallis, Oregon, 97330

Recruiting
Esther VanTil · Contact
John Strother · Principal Investigator

Oncology Associates of Oregon PC

Eugene, Oregon, 97401-8122

Recruiting
Spencer Dandy · Contact
Miho Dougherty · Principal Investigator

Northwest Cancer Specialists

Portland, Oregon, 97210

Recruiting
Jay Andersen · Principal Investigator

Oregon Oncology Specialists Salem

Salem, Oregon, 97301

Recruiting
Kyla Kinney · Contact
Janelle Meyer · Principal Investigator

Consultants In Med Onco And Hema

Drexel Hill, Pennsylvania, 19026

Recruiting
Maureen Lisowski · Contact
Alexander Deak · Principal Investigator

Univ of Pittsburg Med Ctr Pinnacle

Harrisburg, Pennsylvania, 17109

Recruiting
Bridgett West · Contact
Marija Balic · Principal Investigator

Rhode Island Hospital

Providence, Rhode Island, 02903

Recruiting
Janine Grigelevich · Contact
Stephanie Graff · Principal Investigator

Bon Secours St Francis Cancer Center

Greenville, South Carolina, 29607

Recruiting
Christine Sanchez · Contact
Stephen Howard Dyar · Principal Investigator

Lexington Medical Center

West Columbia, South Carolina, 29169

Recruiting
Katharine Madden · Contact
Steven Madden · Principal Investigator

Regional Medical Oncology NC

Wilson, South Carolina, 27893

Recruiting
Merdith Best · Contact
Keith Lerro · Principal Investigator

Sanford USD Medical Center

Sioux Falls, South Dakota, 57104

Recruiting
Allison Watson · Principal Investigator

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting
Madeleine Enos · Contact
Denise A Yardley · Principal Investigator

El Paso Texas Oncology

El Paso, Texas, 79902

Recruiting
Mary Williams · Contact
Ines Sanchez-Rivera · Principal Investigator

Kelsey Seybold Clinic

Houston, Texas, 77025

Recruiting
Sunil Patel · Principal Investigator

University of Texas

Houston, Texas, 77030-4099

Recruiting
Cynthia Tamez · Contact
Jason Mouabbi · Principal Investigator

Texas Oncology P A Plano East

Plano, Texas, 75075

Recruiting
Carlos Taboada · Principal Investigator

Texas Oncology PA Tyler

Tyler, Texas, 75702

Recruiting
Jennifer Castner · Contact
Nanna Sulai · Principal Investigator

Bon Secours Virginia Health System

Midlothian, Virginia, 23114

Recruiting
Mary M Williams · Contact
William Irvin · Principal Investigator

Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting
Patricia Innis-Deleon · Contact
Michael A Danso · Principal Investigator

Kadlec Clinic Hematology and Onco

Kennewick, Washington, 99336

Recruiting
Ying Zhuo · Principal Investigator

Providence Regional Cancer System

Lacey, Washington, 98503

Recruiting
Mijung Lee · Principal Investigator

Valley Medical Center Research

Renton, Washington, 98055

Recruiting
Dione Froman · Contact
Navanshu Arora · Principal Investigator

Northwest Medical Specialties

Tacoma, Washington, 98405

Recruiting
Patricia Walsh · Contact
Sibel Blau · Principal Investigator
Phase IIIb Study of Ribociclib + ET in Early Breast Cancer | Cancerify