RADIANT: Pre-op Radiation With Abemaciclib and Letrozole

NCT06139107 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 042311Pro2023001900
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

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

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

Outcome Measures

Primary Outcomes (1)

• 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)

  The outcome measure aims to characterize the safety and toxicity profile of the study treatment by assessing the occurrence and severity of adverse events (AEs) as measured using the CTCAE v.5. The CTCAE v.5 utilizes a standardized grading scale to assess the severity of adverse events. The scale consists of grades ranging from 1 to 5, with each grade corresponding to a specific level of severity. The grades are: Grade 1 Mild Event is asymptomatic or mild, requiring minimal or no medical intervention. Grade 2 Moderate Event minimal to moderate interference with daily activities, and some medical intervention. Grade 3 Severe Event causes significant interference with daily activities, and medical intervention or treatment is required. Grade 4 Life-threatening or disabling Event poses immediate risk to life or function, requiring urgent medical intervention or treatment. Grade 5 Death Event results in death related to the adverse event.

  From baseline, every six months, to five years

Secondary Outcomes (5)

• Clinical efficacy of the study treatment regimen measured by Rates of Residual Cancer Burden (RCB).

  From baseline, every six months, to five years

• Rate of post-operative complications measured by descriptive statistics

  From baseline, every six months, to five years

• Rate of breast-conserving surgery measured with with a 95% confidence interval for proportions

  From baseline, every six months, to five years

• Rates of residual cancer burden (RCB) as a proportion with 95% confidence interval

  From baseline, every six months, to five years

• Two year invasive disease-free survival (DFS) rate

  From baseline, every six months, to five years

Other Outcomes (1)

• Changes to DNA repair mechanism measured by Harvard/NSABP/Radiation Therapy Oncology Group (RTOG) breast Cosmesis scale

  From baseline, every six months, to five years

Study Arms (1)

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

EXPERIMENTAL

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

Drug: Abemaciclib; Drug: Letrozole

Interventions

Abemaciclib DRUG

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

Also known as: CDK4/6 Inhibitor Therapy.

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

Letrozole DRUG

Letrozole 2.5mg daily

Also known as: Aromatase Inhibitor Therapy.

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

Eligibility Criteria

• Age: 60 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mridula George, MD: lead

Study Sites (4)

RWJBarnabas Health Clara Maas Medical Center

Belleville, New Jersey, 07109, United States

RECRUITING

Cooperman Barnabas Medical Center

Livingston, New Jersey, 07039, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

RWJBarnabas Health - Robert Wood Johnson University Hospital Somerset

Somerville, New Jersey, 08873, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mridula A George, MD

  Cancer Institute of New Jersey Rutgers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mridula A George, MD

CONTACT

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

Mridula A George, MD

CONTACT

Mridula; mridula@cinj.rutgers.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 18, 2023
• Study Start: August 22, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2032
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)