RADIANT: Pre-op Radiation With Abemaciclib and Letrozole

• Status: Recruiting
• Trial end date: 2032-09-30
• Target enrollment: 0
• Participant gender: Female

Summary

This phase 1b study investigates the safety and feasibility of combining pre-operative radiation therapy with Cyclin-Dependent Kinase 4 (CDK4/6) inhibitors in participants with hormone receptor positive/HER2 negative (HR+/HER2-) breast cancer. The study aims to assess the benefits of concurrent use of these treatments in a specific participant population, focusing on their safety and tolerability. The hypothesis is that the combination therapy will be well-tolerated, providing valuable insights into its effectiveness for future clinical applications.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mridula George, MD
• Treatments: Aromatase Inhibitors; Letrozole

Criteria

Inclusion Criteria:

• Histologically and/or cytologically confirmed diagnosis of invasive (ductal, lobular or mixed histology), Clinically inapparent tumor that is not palpable. (cT1-T2N0)disease. Minimum tumor size of 1.5 cm

• Expression of ER or progesterone receptors (PR)and negative expression of HER2 per American Society of Clinical Oncology, (ASCO) Common Alerting Protocol (CAP) guidelines

• Oncotype diagnosis (DX) Breast Recurrence score of less than 25 on core biopsy specimen

• Post-menopausal status defined:

• age <60 with amenorrhea for at least 12 months in the absence of prior chemotherapy, tamoxifen, toremifene, or ovarian suppression and estradiol and FSH (follicle stimulating hormone) in postmenopausal range.

• No clinical suspicion of metastasis disease

• Eastern Cooperative Oncology Group (ECOG) performance status of follicle stimulating hormone (PFS) ≤2

• Eligible to undergo surgery, either lumpectomy or mastectomy for local treatment of the breast cancer

• Able to swallow oral medications

• Adequate organ function for all of the following:

Absolute Neutrophil (ANC) >1.5 x 10/L Platelets >100 x 10/L Hemoglobin >8 g/dL - May receive erythrocyte transfusions to achieve this level Total Bilirubin <1.5 x Upper Limit of Normal (ULN) Alanine Aminotransferase (ATL) and Aspartate Aminotransferase (AST) <3 x ULN

• HR positive/HER2 -negative breast cancers are allowed as long as no other exclusions exist

Exclusion Criteria:

• History of ipsilateral breast cancer

• Prior treatment with CDK4/6 inhibitors or aromatase inhibitors

• History of chest wall or ipsilateral breast radiation

• Inflammatory breast cancer

• Needs neoadjuvant chemotherapy

• Presence of distant metastatic disease

• Contraindication for surgery

• Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg)

• Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study

• Life expectancy < 12 weeks

• History of allergy or hypersensitivity to any of the study drugs

• Any significant medical condition, laboratory abnormality, or psychiatric illness

• Serious and/or uncontrolled preexisting medical condition

• Has had major surgery within 14 days prior to enrollment

• Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research

• Has active systemic bacterial infection

• Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest