Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer

NCT05467891 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN BRE20-468
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 20

Brief Summary

This is an open label, multicenter, single arm phase II study to evaluate the efficacy and safety of ribociclib and ET in patients with locoregional recurrence of HR-positive, HER2-negative breast cancer.

Conditions

Locoregional Recurrence; HER2-negative Breast Cancer; Hormone Receptor-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival (RFS)

  Estimate subsequent recurrence-free survival (RFS) at 3 years for ribociclib when administered with ET (AIs or fulvestrant). RFS is defined as interval from registration until invasive or DCIS recurrence in the ipsilateral breast or locoregionally, invasive recurrence at a distant site, or death from breast cancer or any other cause, whichever occurs first. The censoring time is the completion of study at 6 years (3 years of patient accrual and 3 years of follow up time). The RFS at 3 years will be also treated as the primary endpoint in the power and sample size calculation.

  3 years

Secondary Outcomes (3)

• Distant Metastasis-Free Survival

  3 years

• Overall Survival (OS)

  3 years

• Assess adverse events

  3 months

Study Arms (1)

Investigational Group

EXPERIMENTAL

The drug ribociclib will be taken orally at a dose of 400 mg daily for 21 days out of a 28-day cycle. Ribociclib will be used in combination with ET per physician choice. All new subjects enrolled under the 08JUL2024 protocol or after will receive ribociclib 400mg daily for 21 days out of a 28-day cycle. Subjects receiving 600mg ribociclib under a prior protocol version will be switched to 400mg. Physician's choice of endocrine therapy includes: * 500 mg of fulvestrant received intramuscularly. This will be taken on Day 1 and Day 15 of Cycle 1 and on Day 1 of Cycle 2 and beyond. * 1 mg of anastrozole taken orally daily of the 28 day cycle. * 2.5 mg of letrozole taken orally daily of the 28 day cycle. * 25 mg of exemestane taken orally daily of the 28 day cycle. * Concomitant use with tamoxifen is not allowed. Premenopausal subjects must also be treated with ovarian suppression according to institutional standards or have undergone bilateral oophorectomy.

Drug: Ribociclib; Drug: Fulvestrant; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane

Interventions

Ribociclib DRUG

400 mg orally once daily Days 1-21 (28 day Cycle)

Also known as: Kisqali

Investigational Group

Fulvestrant DRUG

500 mg intramuscularly on Day 1 and 15 of Cycle 1 then Day 1 of Cycle 2+

Also known as: Faslodex

Investigational Group

Anastrozole DRUG

1 mg orally once daily

Also known as: Arimidex

Investigational Group

Letrozole DRUG

2.5 mg orally once daily

Also known as: Femara

Investigational Group

Exemestane DRUG

25 mg orally once daily

Also known as: Aromasin

Investigational Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent (stage II/ main consent) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific screening procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Male or female age ≥ 18 years at the time of consent. NOTE: Both pre- and post-menopausal women are eligible. Post-menopausal status is defined as:
• Prior bilateral oophorectomy
• Age ≥60
• Age \<60 and amenorrhea for the last 12 or more months(in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• If patient is receiving tamoxifen or toremifene, a washout period of 5 half-lives (i.e. 35 days) prior to registration is required (during that period the participant can take AI).
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an 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 and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
• Patients have had adequate local treatment for locoregional recurrence (LRR) of breast cancer.
• Locoregional recurrence is defined as recurrence in the ipsilateral breast, axilla, regional lymph nodes, or chest wall.
• Local treatment is defined as either surgery, radiation therapy, or a combination of both if indicated.
• Adequate local therapy is surgery with negative microscopic margins. Radiation therapy is mandated for patients with microscopically involved margins and recommended for all patients who had not received radiotherapy as part of their primary treatment.
• Patients who have distant metastatic disease will not be eligible.
• Prior treatment with neoadjuvant and adjuvant chemotherapy and ET is allowed.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patient with a known hypersensitivity to any of the excipients of ribociclib.
• Patient who has received prior CDK4/6 inhibitor for recurrent disease. Patients who received a CDK4/6 inhibitor in the adjuvant setting may participate if they have been off therapy for at least 1 year prior to diagnosis of recurrent disease.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
• Pregnant or breastfeeding or planning to become pregnant during the trial (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
• Patients with distant metastases of breast cancer beyond regional lymph nodes as defined by AJCC (8th edition).
• Treatment with any investigational drug within 30 days prior to registration or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. Enrollment or planned enrollment in another study that does not involve an investigational drug will be allowed at the discretion of the treating investigator.
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, HIV, active untreated or uncontrolled fungal, bacterial or viral infections, etc.). Testing to be done at investigator's discretion.
• 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 (CABG) within 6 months prior to study entry
• Documented cardiomyopathy
• History of Left Ventricular Ejection Fraction (LVEF) \< 50%
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

Sponsors & Collaborators

• Oana Danciu: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of Arizona

Phoenix, Arizona, 85004, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

ACTIVE NOT RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Michigan Health-West

Wyoming, Michigan, 49519, United States

TERMINATED

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

RECRUITING

New York University Clinical Cancer Center

New York, New York, 10016, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Interventions

ribociclib; Fulvestrant; Anastrozole; Letrozole; exemestane

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Oana Danciu, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oana Danciu, MD

CONTACT

312-996-1581; ocdanciu@uic.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 21, 2022
• Study Start: September 13, 2022
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)