Recruiting
Phase 1

Abemaciclib & Letrozole

Sponsor:

Mridula George, MD

Code:

NCT06139107

Conditions

Breast Cancer

Eligibility Criteria

Sex: Female

Age: 60+

Healthy Volunteers: Not accepted

Interventions

Abemaciclib

Letrozole

Study Details

Brief 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.

Conditions

Breast Cancer

Study ID

NCT06139107

Start date

Aug 22, 2024

Status verified date

Nov, 2025

Completion date

Sep 30, 2032

Anticipated

Primary completion date

Sep 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 60+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

15 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Combined Pre-Operative Therapy with Abemaciclib, Letrozole, and Radiation in HR+/HER2- Breast Cancer

Part A:

  • 28-day treatment cycle based on abemaciclib
  • Abemaciclib 150mg BID (twice a day).
  • Letrozole 2.5mg daily and Abemaciclib 150mg twice a day for three cycles prior to undergoing radiation therapy.
  • On-treatment biopsy conducted between cycle 3, day 16, and cycle 4, day 1.
  • This occurs two weeks prior to transitioning to Part B.

Dose Level 0 150mg Twice daily with at least 6 hours between doses Dose Level 1 100mg Twice daily with at least 6 hours between doses Dose Level 2 50mg Twice daily with at least 6 hours between doses

Part B:

  • Continue treatment from Part A, 28-day cycle based on abemaciclib.
  • Abemaciclib 150mg BID (twice a day) with letrozole 2.5mg daily.
  • Part B focuses on the administration of radiation therapy following the three cycles of combined abemaciclib and letrozole.
  • Targeted radiation treatment.

Part C:

  • Two cycles of abemaciclib, 150mg twice a day.
  • Letrozole 2.5mg daily.

Part D:

Surgery

Interventions

Abemaciclib

150mg twice a day for 3 cycles prior to radiation.

Letrozole

Letrozole 2.5mg daily

Primary outcome measure

  • Safety and tolerability of the combination of abemaciclib and radiation as assessed by adverse events (AEs). Using Common Terminology Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: From baseline, every six months, to five years ]

Central Contacts and Locations

Central contacts

Mridula A George, MD

732-235-9081mridula@cinj.rutgers.edu

Mridula A George, MD

Mridulamridula@cinj.rutgers.edu

Locations

RWJBarnabas Health Clara Maas Medical Center

Recruiting

Belleville, New Jersey, United States, 07109

Contacts

Mridula George, MD

732-235-9809mridula@cinj.rutgers.edu

Kassie DiOrio

732-454-9795kassie.diorio@rutgers.edu

Cooperman Barnabas Medical Center

Recruiting

Livingston, New Jersey, United States, 07039

Contacts

Mridula George, MD

7322358909mridula@cinj.rutgers.edu

Kassie DiOrio

7324549795kassie.diorio@rutgers.edu

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08903

Contacts

Mridula George, MD

7322358909mridula@cinj.rutgers.edu

Kassie DiOrio

7324549795kassie.diorio@rutgers.edu

RWJBarnabas Health - Robert Wood Johnson University Hospital Somerset

Recruiting

Somerville, New Jersey, United States, 08873

Contacts

Mridula George, MD

732-235-8909mridula@cinj.rutgers.edu

Kassie DiOrio

7324549795kassie.diorio@rutgers.edu

More Information

Sponsor

Mridula George, MD

Last update posted

Nov 14, 2025

Last verified

Nov, 2025

Keywords

  • Pre-op radiation
  • CDK4/6 inhibitors
  • Positive/HER2 negative (HR+/HER2-) breast cancer
  • Abemaciclib
  • Combination of abemaciclib and radiation
  • Post-menopausal women
  • Node-negative hormone-receptor (HR) positive/ human epidermal growth factor receptor 2 (HER2)
  • Negative breast cancers
  • Phase 1b
  • Letrozole and abemaciclib

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mridula George, MD on 2025-11-14.