Overview

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

Status:
Recruiting
Trial end date:
2030-03-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Michigan Rogel Cancer Center
Criteria
Inclusion Criteria:

- 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

- Patient must have the following laboratory values within normal limits or
corrected to within normal limits with supplements before the first dose of study
medication:

- Potassium

- Magnesium

- Total Calcium (corrected for serum albumin)

- QTcF interval at screening EKG ≤ 450ms (QT interval using Fridericia's correction).

- Mean resting heart rate 50-90 bpm (determined from the EKG).

- Ability to swallow study drug (Ribociclib).

- ECOG Performance Status 0-1 (Karnofsky > 60%).

- Availability of archival tumor tissue from surgical specimen.

- Ability to understand and willingness to sign informed consent.

- Women of childbearing potential must have confirmed negative pregnancy test (urine or
serum) within 14 days of initiation of study treatment.

Exclusion Criteria:

- 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.

- 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 trial or compromise compliance with the protocol
(e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other
significant liver disease, active untreated or uncontrolled fungal, bacterial or viral
infections, active infection requiring systemic antibacterial therapy, etc.) or limit
life expectancy to ≤5 years. Questions regarding inclusion of individual subjects
should be directed to Drs. Cobain and Speers ([email protected] and
[email protected]).

- 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 impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the oral trial treatments (e.g. uncontrolled
ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption
syndrome, or small bowel resection).

- Patients must not receive any additional anti-cancer therapy or investigational agents
during study therapy. Anti-cancer therapies include chemotherapy and endocrine
therapy.

- 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.