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NCT07391774PHASE3Recruiting

Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial

National Cancer Institute (NCI)

Start Date

2/14/2027

Completion Date

7/31/2029

Summary

This phase III trial compares standard of care hormone therapy plus ribociclib to chemotherapy followed by hormone therapy plus ribociclib for the treatment of patients with high anatomic stage breast cancer with low risk of the cancer returning (low risk recurrence). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy, with letrozole, anastrozole or exemestane, lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hormone therapy plus ribociclib may work as well as chemotherapy followed by hormone therapy plus ribociclib for the treatment of high anatomic stage breast cancer with low recurrence risk.

Detailed Description

PRIMARY OBJECTIVE: I. To determine whether optimal adjuvant endocrine therapy with CDK4/6 inhibitor is non-inferior to adjuvant chemotherapy followed by optimal endocrine therapy with CDK4/6 inhibitor as evaluated by invasive breast cancer-free survival (iBCFS). SECONDARY OBJECTIVES: I. To compare 5-year invasive disease-free survival (iDFS), distant disease-free survival (DDFS), distant recurrence-free survival (DRFS), recurrence-free interval (RFI), overall survival (OS), and breast cancer-specific survival (BCSS) in patients who receive adjuvant chemotherapy versus patients who do not. II. To compare the short-term and long-term toxicity profiles of each arm. EXPLORATORY OBJECTIVE: I. To create a biorepository of tumor tissue and peripheral blood biospecimens for future research. OUTLINE: STEP 0: Patients undergo Oncotype DX risk recurrence testing. Patients with an Oncotype DX recurrence score of 0-25 proceed to step 1. Patients with a recurrence score of 26-100 do not continue on the study. STEP 1: Patients are randomized to 1 of 2 arms. ARM A: Patients receive their physician's choice of standard of care chemotherapy. Patients then receive their physician's choice of standard of care hormone therapy with letrozole, anastrozole, or exemestane orally (PO) once daily (QD) on days 1-28 of each cycle, as well as ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days for at least 60 months for hormone therapy and up to 3 years for ribociclib, in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan, bone scan, or fludeoxyglucose (FDG) positron emission tomography (PET)-CT scan and may optionally undergo blood sample collection throughout the study. ARM B: Patients receive their physician's choice of standard of care hormone therapy with letrozole, anastrozole, or exemestane PO QD on days 1-28 of each cycle and ribociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days for at least 60 months for hormone therapy and up to 3 years for ribociclib, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, bone scan, or FDG PET-CT scan and may optionally undergo blood sample collection throughout the study. Patients are followed every 3 months for 12 months from randomization, every 6 months for years 1-5 from randomization, then every 12 months for years 5-10 from randomization.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * STEP 0: Patient must be ≥ 18 years of age * STEP 0: Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days prior to Step 0 pre-registration * STEP 0: Patient must be a postmenopausal woman or a man * NOTE: Menopause can be determined by any of the following: * Prior bilateral oophorectomy * Age ≥ 60 years * Age \< 60 years with amenorrhea for ≥ 12 months and estradiol and follicle stimulating hormone (FSH) levels in the postmenopausal range * NOTE: FSH and estradiol levels should be repeated as clinically indicated to ensure menopausal status in patients with breast cancer with chemotherapy-induced amenorrhea * STEP 0: Patient must meet one of the following staging criteria postoperatively according to American Joint Committee on Cancer (AJCC) 8th edition criteria * pT0-T3 with 3 positive ipsilateral lymph nodes (micro-or macrometastatic disease) and no planned axillary lymph node dissection after definitive surgery in the breast and axilla with curative intent. * pT0-T3 with N2 or N3 * pT3 with N0-N3 * NOTES: * Patients with T4 breast cancer are not eligible. * Positive isolated tumor cells (ITCs) in axillary nodes without micro- or macrometastasis are considered N0 for eligibility purposes. * ITC does not contribute to nodal count for staging purposes * STEP 0: Patient must have a primary breast tumor that is estrogen receptor (ER) positive with \> 10% ER expression by immunohistochemistry (IHC) as per 2020 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Estrogen Receptor Testing Guideline. * NOTE: ER 1-10% are reported as ER low positive. These tumors have less endocrine-sensitive disease and are not eligible) * STEP 0: Patient must have a primary breast tumor that is HER2-negative by current ASCO/CAP guidelines utilizing immunohistochemistry and/or fluorescence in situ hybridization (FISH) * STEP 0: Patient may have multicentric or multifocal breast cancer if the highest stage tumor meets eligibility criteria outlined above, and the tumor sites are felt to represent a single disease process by local pathology or other sites of disease are also ER-positive (\> 10%) and HER2 negative, if such testing is completed. If local pathology feels that multicentric or multifocal disease may represent distinct disease processes repeat disease receptor testing is required other sites of disease must also be also ER-positive (\> 10%) and HER2-negative * STEP 0: For patients who have undergone a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection * STEP 0: For patients who have undergone mastectomy, the margins must be free of residual gross tumor. Patients with microscopic positive margins are eligible if post-mastectomy radiation treatment (RT) of the chest wall will be administered * STEP 0: Patient must have undergone axillary staging with sentinel lymph node biopsy (SLNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND) * STEP 0: Patient must have no evidence of locoregional or distant metastatic disease by clinical history and physical exam. Treating physician can consider additional imaging evaluation per National Comprehensive Cancer Network (NCCN) guidelines and/or institutional practice * STEP 0: Patient must be able to have Oncotype DX testing performed. * If Oncotype DX testing was previously performed, the results of Recurrence Score (RS) must be available and must meet Step 1 eligibility criteria. * If Oncotype DX testing was not performed yet, tissue from the core, excisional biopsy or surgical specimen of the tumor lesion must be available and must be shipped to Exact Sciences for determination of the Oncotype DX Recurrence Score (RS) for eligibility and stratification. * NOTE: Exact Sciences will notify the submitting institution of Recurrence Score results within two (2) weeks of receipt of the tumor specimen. Institutions will receive an email notification of eligibility status once Recurrence Score results are entered into Rave by the submitting institution * STEP 0: Patient must have had their final cancer surgery for breast cancer (including re-excision of margins) less than 16 weeks prior to Step 0 Pre-Registration. * NOTE: This excludes additional surgery for reconstructive purposes * STEP 0: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * STEP 0: Patients with synchronous DCIS or LCIS are eligible * STEP 0: Patient with prior history of ER-negative DCIS diagnosed at least 5 years prior to Step 0 Pre-Registration without evidence of recurrence are eligible * STEP 0: Patient must not have a prior history of invasive ER-positive breast cancer. Patients with a history of ER-negative breast cancer are eligible if they were diagnosed at least 5 years prior to Step 0 Pre-Registration and have had no evidence of recurrence * STEP 0: Patients must not have received prior endocrine therapy such as tamoxifen, raloxifene, or aromatase inhibitors for chemoprevention within 5 years prior to Step 0 Pre-Registration with the exception of a short course of endocrine therapy of less than 6 weeks duration prior to Step 0 Pre-Registration. * NOTE: The Oncotype Dx for study eligibility must be performed on specimen obtained prior to initiation of any endocrine therapy * STEP 0: Patient must not be concurrently using systemic hormone replacement therapy (HRT). If receiving HRT at the time of breast cancer diagnosis, this must be discontinued prior to Step 0 Pre-Registration with appropriate washout * STEP 0: Absolute neutrophil count (ANC) ≥ 1,500/µL (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Platelets ≥ 100,000/µL (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Total bilirubin ≤ institutional upper limit of normal (ULN) or \< 1.5 x ULN for patients who have a bilirubin elevation in patients with well documented Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × institutional ULN (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/minute/1.73 m\^2 (obtained ≤ 28 days prior to Step 0 Pre-Registration) * STEP 0: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 0 Pre-Registration are eligible for this trial * STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * STEP 0: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * STEP 0: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better * STEP 0: Patient must have a standard 12-lead electrocardiogram (ECG) within 28 days prior to Step 0 Pre-Registration, documenting: * QT interval using Fridericia's correction (QTcF) \< 450 msec. * Resting heart rate 50-90 beats per minute (determined from the ECG) * STEP 0: Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible * STEP 0: Patient must not have comorbidities considered a safety risk for standard adjuvant chemotherapy, endocrine therapy or CDK4/6 inhibitor as per Investigator's discretion * STEP 0: Patient must not have a contraindication to adjuvant chemotherapy based on treating physician's discretion * STEP 0: Patient must not have received prior chemotherapy for this malignancy * STEP 0: Patient must not have received prior CDK4/6 inhibitor * STEP 0: Patient must not have a known contraindication to ribociclib per current Food and Drug Administration (FDA) indication * STEP 0: Patient must not have a known hypersensitivity to any of the excipients of ribociclib and/or endocrine therapy (ET) (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy) * STEP 0: Males must not expect to father children and males and their partners must be willing to use highly effective methods of contraception while on protocol treatment. Males must not donate sperm while on protocol treatment and for at least 12 weeks following the last dose of protocol treatment. Highly effective methods include the following: * Intrauterine device * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence If the highly effective contraceptive methods are contraindicated or strictly declined by the patient, or in the event of sexual activity of low frequency, a combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier methods) is also considered an acceptable birth control method. Local regulation/guidelines are to be followed with regard to highly effective birth control method, if more restrictive * STEP 1: Patient must meet all Step 0 Pre-Registration eligibility criteria at the time of their Step 1 randomization * STEP 1: Patient must not have had any major surgery or radiotherapy within 14 days prior to Step 1 randomization * STEP 1: Patient must have a Recurrence Score (RS) of 0-25 from Oncotype DX testing from diagnostic biopsy or surgical specimen as reported by the Exact Sciences assay

Interventions

DRUG

Anastrozole

PROCEDURE

Biospecimen Collection

PROCEDURE

Bone Scan

DRUG

Chemotherapy

PROCEDURE

Computed Tomography

DRUG

Exemestane

DRUG

Letrozole

PROCEDURE

Oncotype DX Breast Cancer Assay

PROCEDURE

Positron Emission Tomography

DRUG

Ribociclib Succinate

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Conditions

Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIC Breast Cancer AJCC v8Estrogen Receptor-Positive Breast CarcinomaHER2-Negative Breast Carcinoma

Locations

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

Jonesboro, Arkansas 72401

United States

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California 94704

United States

Palo Alto Medical Foundation Health Care

Palo Alto, California 94301

United States

Sutter Roseville Medical Center

Roseville, California 95661

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

California Pacific Medical Center-Pacific Campus

San Francisco, California 94115

United States

Mills Health Center

San Mateo, California 94401

United States

Sutter Solano Medical Center/Cancer Center

Vallejo, California 94589

United States

Stamford Hospital/Bennett Cancer Center

Stamford, Connecticut 06904

United States

Helen F Graham Cancer Center

Newark, Delaware 19713

United States

Medical Oncology Hematology Consultants PA

Newark, Delaware 19713

United States

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho 83814

United States

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho 83854

United States

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho 83864

United States

Illinois CancerCare-Bloomington

Bloomington, Illinois 61704

United States

Illinois CancerCare-Canton

Canton, Illinois 61520

United States

SIH Cancer Institute

Carterville, Illinois 62918

United States

Illinois CancerCare-Carthage

Carthage, Illinois 62321

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois 62526

United States

Decatur Memorial Hospital

Decatur, Illinois 62526

United States

Illinois CancerCare-Eureka

Eureka, Illinois 61530

United States

Illinois CancerCare-Galesburg

Galesburg, Illinois 61401

United States

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois 61443

United States

Illinois CancerCare-Macomb

Macomb, Illinois 61455

United States

SSM Health Good Samaritan

Mount Vernon, Illinois 62864

United States

Cancer Care Center of O'Fallon

O'Fallon, Illinois 62269

United States

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois 62269

United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois 61350

United States

Illinois CancerCare-Pekin

Pekin, Illinois 61554

United States

Illinois CancerCare-Peoria

Peoria, Illinois 61615

United States

Illinois CancerCare-Peru

Peru, Illinois 61354

United States

Illinois CancerCare-Princeton

Princeton, Illinois 61356

United States

Southern Illinois University School of Medicine

Springfield, Illinois 62702

United States

Springfield Clinic

Springfield, Illinois 62702

United States

Springfield Memorial Hospital

Springfield, Illinois 62781

United States

Illinois CancerCare - Washington

Washington, Illinois 61571

United States

Mary Greeley Medical Center

Ames, Iowa 50010

United States

McFarland Clinic - Ames

Ames, Iowa 50010

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa 50023

United States

Saint Anthony Regional Hospital

Carroll, Iowa 51401

United States

Mercy Hospital

Cedar Rapids, Iowa 52403

United States

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa 52403

United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa 50325

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa 50309

United States

Broadlawns Medical Center

Des Moines, Iowa 50314

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa 50314

United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa 50314

United States

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa 50501

United States

UI Healthcare Mission Cancer and Blood - Fort Dodge

Fort Dodge, Iowa 50501

United States

McFarland Clinic - Marshalltown

Marshalltown, Iowa 50158

United States

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa 50263

United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan 48114

United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan 48188

United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan 48118

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan 48154

United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan 48197

United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle

Columbus, Mississippi 39705

United States

Baptist Cancer Center-Grenada

Grenada, Mississippi 38901

United States

Baptist Memorial Hospital and Cancer Center-Union County

New Albany, Mississippi 38652

United States

Baptist Memorial Hospital and Cancer Center-Oxford

Oxford, Mississippi 38655

United States

Baptist Memorial Hospital and Cancer Center-Desoto

Southhaven, Mississippi 38671

United States

Bozeman Health Deaconess Hospital

Bozeman, Montana 59715

United States

Benefis Sletten Cancer Institute

Great Falls, Montana 59405

United States

Community Medical Center

Missoula, Montana 59804

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Southeastern Medical Oncology Center-Clinton

Clinton, North Carolina 28328

United States

Southeastern Medical Oncology Center-Goldsboro

Goldsboro, North Carolina 27534

United States

Southeastern Medical Oncology Center-Jacksonville

Jacksonville, North Carolina 28546

United States

Lexington Medical Center

West Columbia, South Carolina 29169

United States

Baptist Memorial Hospital and Cancer Center-Collierville

Collierville, Tennessee 38017

United States

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee 38120

United States