RADIANT: Pre-op Radiation With Abemaciclib and Letrozole

NCT ID: NCT06139107

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-22
• Study Completion Date: 2032-09-30

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.

Detailed Description

In this phase 1b study, researchers will conduct a comprehensive investigation into the concurrent administration of pre-operative radiation therapy and CDK4/6 inhibitors in a carefully selected participant population diagnosed with hormone receptor positive/HER2 negative (HR+/HER2-) breast cancer. The study aims to elucidate the safety and feasibility of this combination therapy. Participants will undergo rigorous evaluation and monitoring to assess the potential synergistic effects and adverse reactions resulting from the simultaneous use of radiation and CDK4/6 inhibitors. Detailed clinical assessments, imaging studies, and laboratory analyses will be performed to monitor treatment response and any associated side effects.

The study hypothesizes that this combination therapy will be well-tolerated, paving the way for further investigations into its efficacy. By closely examining the outcomes and tolerability of this treatment approach, researchers aim to contribute valuable data to the understanding of novel therapeutic strategies for HR+/HER2- breast cancer. The detailed analysis of participant responses and safety profiles in this study will provide crucial insights for optimizing future clinical interventions and improving outcomes for individuals diagnosed with this specific breast cancer subtype.

Conditions

Breast Cancer

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

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

Letrozole

Intervention Type: DRUG

Letrozole 2.5mg daily

Interventions

Abemaciclib

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

Intervention Type: DRUG

Letrozole

Letrozole 2.5mg daily

Intervention Type: DRUG

Other Intervention Names

CDK4/6 Inhibitor Therapy.; Aromatase Inhibitor Therapy.

Eligibility 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

• Minimum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mridula George, MD

OTHER

Sponsor Role: lead

Responsible Party

Mridula George, MD

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mridula A George, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute of New Jersey Rutgers

Locations

RWJBarnabas Health Clara Maas Medical Center

Belleville, New Jersey, United States

Site Status: RECRUITING

Cooperman Barnabas Medical Center

Livingston, New Jersey, United States

Site Status: RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status: RECRUITING

RWJBarnabas Health - Robert Wood Johnson University Hospital Somerset

Somerville, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mridula A George, MD

Role: CONTACT

Phone: 732-235-9081

Email: mridula@cinj.rutgers.edu

Mridula A George, MD

Role: CONTACT

Phone: Mridula

Email: mridula@cinj.rutgers.edu

Facility Contacts

Mridula George, MD

Role: primary

Kassie DiOrio

Role: backup

Mridula George, MD

Role: primary

Kassie DiOrio

Role: backup

Mridula George, MD

Role: primary

Kassie DiOrio

Role: backup

Mridula George, MD

Role: primary

Kassie DiOrio

Role: backup

Other Identifiers

042311

Identifier Type: -

Identifier Source: org_study_id

Pro2023001900

Identifier Type: OTHER

Identifier Source: secondary_id