A Phase 1B Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, Node Positive, HR+/HER2- Breast Cancer
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.
• 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.