Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, HR+/HER2- Breast Cancer

NCT05996107 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: UMCC 2022.071HUM00231659
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to determine the safety, tolerability and dose of Ribociclib when combined with adjuvant radiation in women with high-risk ER+ breast cancer. Once enrolled on study, patients will begin treatment with Ribociclib 400 mg daily at the same time as they initiate standard of care adjuvant radiation therapy- 50 Gy in 25 fractions or 42.56 Gy in 16 fractions +/- 10 Gy boost including comprehensive nodal. Paitents will continue treatment with Ribociclib for up to 6 weeks.

Conditions

Breast Cancer

Keywords

HR+/HER2-; Node positive; High-Risk breast cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) of ribociclib administered concurrently with adjuvant RT 1 month post last RT dose

  Safety evaluations will be based on the incidence, intensity, and type of adverse events, and clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results. Safety variables will be tabulated and presented for all patients in the study. Exposure to study drug and reasons for discontinuation of study treatment will be tabulated.

  up through 30 days after the last dose of study drug or radiotherapy

Secondary Outcomes (5)

• Cumulative incidence of local failure (i.e. local recurrence events)

  up through 2 years after completion of protocol therapy

• Local failure-free survival

  up through 2 years after completion of protocol therapy

• Recurrence-free survival

  up through 2 years after completion of protocol therapy

• Overall survival

  up through 2 years after completion of protocol therapy

• Disease free survival

  up through 2 years after completion of protocol therapy

Study Arms (1)

RT + Ribociclib

EXPERIMENTAL

All patients will be treated with Ribociclib and standard of care radiation therapy

Drug: Ribociclib; Radiation: Postoperative Radiation Therapy

Interventions

Ribociclib DRUG

400 mg daily with a possibly dose reduction to 200 mg daily if required

Also known as: Kisqali

RT + Ribociclib

Postoperative Radiation Therapy RADIATION

50 Gy in 25 fractions or 42.56 Gy in 16 fraction +/- 10 Gy boost including comprehensive nodal

RT + Ribociclib

Eligibility Criteria

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

You may qualify if:

• ER and/or PR-positive (≥ 1% positivity as determined by local pathology laboratory), HER2-negative breast cancer with \> 3 lymph nodes involved on sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) OR have between 1-3 lymph nodes involved AND have T3 disease OR have between 1-3 lymph nodes involved and grade 3 breast cancer.
• Age ≥ 18
• Patients must have undergone gross total excision of all locoregional disease with negative margins (i.e. no tumor on ink). At least 21 days must elapse between surgical treatment for breast cancer and initiation of study treatment.
• Patients must have completed chemotherapy (either in neoadjuvant or adjuvant setting). If received adjuvant chemotherapy, chemotherapy must have completed at least 21 days prior to initiation of study treatment.
• Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and surgical side effects following definitive breast surgery except for neuropathy and alopecia
• Adequate baseline hematologic, hepatic and renal function as indicated below:
• Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by central laboratory for eligibility):
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 9.0 g/dL
• INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug)
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula
• Total bilirubin \< ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.
• Aspartate transaminase (AST) \< 2.5 × ULN, except for patients with liver metastasis, who are only included if the AST is \< 5 × ULN
• Alanine transaminase (ALT) \< 2.5 × ULN, except for patients with liver metastasis, who are only included if the ALT is \< 5 × ULN

You may not qualify if:

• Prior history of radiation therapy to the chest wall and/or regional nodes is not allowed (but prior radiation therapy to other sites is permissible).
• Prior history of CDK4/6 inhibitor therapy.
• Patients who are pregnant or breastfeeding.
• Because radiation is known to be teratogenic, women of childbearing potential must have a documented negative pregnancy test performed prior to the start of study therapy (as above) and agree to use adequate contraception (hormonal or double barrier method of birth control; vasectomized partner; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patient with distant metastases of breast cancer beyond regional lymph nodes and/or evidence of breast cancer recurrence prior to study enrollment.
• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (3)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Michigan Health West

Wyoming, Michigan, 49519, United States

RECRUITING

UHCMC Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Erin Cobain, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

• Corey Speers, MD, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 16, 2023
• Study Start: February 27, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)