A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer

Running, not enrolling · Phase 3

Conditions studied: Early Breast Cancer

In brief

A phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with Endocrine Therapy (ET) as an adjuvant treatment in women and men with Hormone Receptor positive (HR+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) Early Breast Cancer (EBC).

Key facts

Study ID

NCT03701334

Run by

Novartis Pharmaceuticals

People needed

5101

Starts

2018-12-07

Expected to finish

2030-05-29

Last updated by the study team

2026-04-01

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed and dated Patient Informed Consent Form (PICF) obtained prior to any trial-specific screening procedure.
• Patient is ≥ 18 years-old at the time of PICF signature.
• Patient is female with known menopausal status at the time of randomization or initiation of adjuvant ET (whichever occurs earlier), or male.
• Postmenopausal status is defined as:
• Patient underwent bilateral oophorectomy, or
• Age ≥ 60 years, or
• Age < 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Follicle-stimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges.
• If taking tamoxifen or toremifene and age <60 years, then FSH and plasma estradiol level in postmenopausal ranges.
• Notes
• In women who are premenopausal at the beginning of adjuvant chemotherapy, amenorrhea is not a reliable indicator of menopausal status as ovarian function may still be intact or resume despite anovulation/amenorrhea. For these women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol per local clinical guidelines are required for determination of postmenopausal status.
• All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial.
• Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis (i.e. date of the pathology report that confirmed the BC diagnosis) within 18 months prior to randomization. Patient with a multicentric and/or multifocal tumor is eligible if all histopathologically examined lesions meet the pathologic criteria in inclusion criteria 5 and 6.
• Patient has breast cancer that is positive for ER and/or PgR according to the local laboratory as determined on the most recently analyzed tissue sample.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory).
• Patient (except those enrolled in China) has available archival tumor tissue from the surgical specimen, for submission to a central laboratory (Note: in patients that underwent neoadjuvant systemic therapy and had a pathologic complete response, archival tumor tissue at the time of the initial diagnosis or before the administration of neoadjuvant therapy is mandatory).
• Patient, 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
• Anatomic Stage Group IIA (subset)
• Notes:
• For patients whose tumors are Anatomic Stage IIA, N0:
• If Grade is 1 or unknown (Gx), patient is not eligible.
• If Grade 2, the gene expression test results (by Oncotype DX, Prosigna/PAM50, MammaPrint or EndoPredict EPclin) or Ki67 levels should be used if obtained as per local practice (i.e. are not mandatory for the purpose of the trial). Results must be available at screening.
• Patients that received neoadjuvant treatment must meet the above criteria (for stage, and if Stage IIA, N0, also for grade and Ki67 or gene expression test) in any presurgical staging/sample and/or in the surgical specimen.
• Categorization into the AJCC 8th edition Anatomic Stage Groups requires determination of the T, N and M categories. ALND is the preferred method for axillary lymph node staging, however SLN dissection can be used to determine the N category in the following cases:

You may not qualify if…

• Patient has received any CDK4/6 inhibitor.
• Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last 2 years prior to randomization. Patient is concurrently using hormone replacement therapy.
• Patient has received prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for epirubicin.
• Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy).
• Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
• Patient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET (see Inclusion Criterion #12).
• Patient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization.
• Patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies to a NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03 Grade ≤1 at day of randomization. Exceptions to this criterion: patients with any grade of alopecia, amenorrhea, grade 2 neuropathy are allowed to enter the trial or other toxicities not considered a safety risk for the patient as per Investigator's discretion, are allowed to enter the trial.
• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Note: Patients with adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible.
• Patient has known history of human immunodeficiency virus (HIV) infection (testing is not mandatory, unless required by local regulation).
• Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to trial entry.
• Documented cardiomyopathy.
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory)
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment).
• Inability to determine the QTcF interval.
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block).
• Uncontrolled arterial hypertension with systolic blood pressure > 160 mmHg.
• Patient is currently receiving any of the following substances within 7 days before randomization:
• Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummellos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5
• Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment.

Where it is running

• Cancer Treatment Centers of America — Goodyear, Arizona, United States
• St Bernards Medical Center — Jonesboro, Arkansas, United States
• Comprehensive Blood and Cancer — Bakersfield, California, United States
• UCLA Beverly Hills — Beverly Hills, California, United States
• UCLA Burbank — Burbank, California, United States
• Encino Research Center — Encino, California, United States
• St. Jude Heritage Medical Group — Fullerton, California, United States
• UCLA Hematology Oncology — Laguna Hills, California, United States
• Southern CA Oncology Rsrch Alliance — Los Angeles, California, United States
• Stanford University Medical Center — Palo Alto, California, United States
• UCLA Pasadena HC Hemato Onco — Pasadena, California, United States
• UCLA Porter Ranch Hemato and Onco — Porter Ranch, California, United States
• Cancer Care Associates Medical Grp — Redondo Beach, California, United States
• Sharp Memorial Hospital — San Diego, California, United States
• UCSF — San Francisco, California, United States
• Central Coast Medical Oncology Corporation — Santa Maria, California, United States
• UCLA Santa Monica Hematology Oncology — Santa Monica, California, United States
• Lundquist Inst BioMed at Harbor — Torrance, California, United States
• UCLA Valencia — Valencia, California, United States
• Valley Breast Care — Van Nuys, California, United States
• UCLA Cancer Center Westlake Village — Westlake Village, California, United States
• University Of Colorado Hospital — Aurora, Colorado, United States
• Rocky Mountain Cancer Centers — Denver, Colorado, United States
• Hospital of Central Connecticut — New Britain, Connecticut, United States
• University of Alabama at Birmingham-Kirklin Clinic — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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