Pre-op Radiation + Abemaciclib + Letrozole for Breast Cancer

Recruiting at 3 trial locations

Overseen By Mridula George, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Rutgers, The State University of New Jersey

Must be taking: CDK4/6 inhibitors

Must not be taking: CDK4/6 inhibitors, Aromatase inhibitors

Disqualifiers: Metastatic disease, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for hormone receptor positive/HER2 negative (HR+/HER2-) breast cancer. Researchers aim to determine if radiation therapy, combined with Abemaciclib (a targeted cancer therapy) and Letrozole (a hormone therapy), is safe and manageable before surgery. The goal is to assess the effectiveness and tolerability of this combination. This trial may suit post-menopausal women with a breast tumor that isn't easily felt, hasn't spread, who plan to have surgery, and can swallow pills. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on CDK4/6 inhibitors or aromatase inhibitors, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib, when combined with letrozole, has been tested for safety in people with breast cancer. In past studies, this combination was generally well-tolerated, with most patients experiencing mild to moderate side effects such as diarrhea and tiredness. Serious side effects occurred less frequently.

The FDA has already approved abemaciclib for certain types of breast cancer, confirming its safety for those conditions. Adding radiation is a newer approach, but early studies indicate that these treatments can be combined safely. The aim is to determine if this combination can be effective before surgery.

While these treatments have been tested both separately and together, this specific approach remains under study. However, early evidence suggests that most people can tolerate the combination well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abemaciclib, Letrozole, and pre-operative radiation therapy for breast cancer because this approach targets the cancer in a unique way. Unlike standard treatments like surgery followed by chemotherapy or hormone therapy alone, this regimen uses Abemaciclib, a CDK4/6 inhibitor, together with Letrozole, an aromatase inhibitor, to potentially shrink tumors before surgery. This pre-operative strategy could make tumors more manageable and increase the effectiveness of surgical removal. Additionally, introducing radiation therapy earlier in the treatment process may enhance the overall response and improve long-term outcomes. This innovative combination holds promise for more personalized and effective treatment options for HR+/HER2- breast cancer patients.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that combining Abemaciclib and Letrozole may effectively treat hormone receptor-positive, HER2-negative breast cancer. In this trial, participants will receive a pre-operative therapy combining Abemaciclib, Letrozole, and radiation. Abemaciclib blocks proteins that promote cancer cell growth, potentially slowing or stopping cancer progression. Studies have found this drug combination particularly effective in aggressive cases. Letrozole lowers estrogen levels, further slowing cancer growth. Early results suggest that using these drugs with radiation before surgery may enhance treatment effectiveness. Although more research is needed, these promising findings offer hope for improved treatment outcomes. ^{2 5 6 7 8}

Who Is on the Research Team?

Mridula George, MD

Principal Investigator

Cancer Institute of New Jersey Rutgers

Are You a Good Fit for This Trial?

This trial is for individuals with HR+/HER2- breast cancer who can take oral meds, are surgery candidates (lumpectomy or mastectomy), have a tumor size of at least 1.5 cm, and meet specific hormone receptor criteria. They must not be suspected of having metastatic disease, should have an ECOG performance status ≤2, and certain blood levels must be within specified ranges.

Inclusion Criteria

My breast cancer recurrence score is below 25.

My cancer has not spread to other parts of my body.

I am a candidate for surgery to remove my breast cancer.

Exclusion Criteria

I need chemotherapy before surgery.

I have had breast cancer in the same breast before.

I have had radiation therapy on the same side as my current breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive Abemaciclib and Letrozole for three cycles prior to radiation therapy

12 weeks

Regular visits for monitoring and on-treatment biopsy between cycle 3, day 16, and cycle 4, day 1

Treatment Part B

Continuation of Abemaciclib and Letrozole with the addition of radiation therapy

4 weeks

Regular visits for radiation therapy administration

Treatment Part C

Two additional cycles of Abemaciclib and Letrozole

8 weeks

Surgery

Participants undergo surgery following treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up visits every six months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Letrozole

Trial Overview

The RADIANT study tests the safety and potential benefits of combining pre-op radiation therapy with Abemaciclib and Letrozole in treating early-stage breast cancer. It's designed to see if this combo is tolerable and could inform future treatment effectiveness.

How Is the Trial Designed?

Group I: Combined Pre-Operative Therapy with Abemaciclib, Letrozole, and Radiation in HR+/HER2- Breast Cancer Experimental Treatment 2 Interventions

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

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Mridula George, MD

Lead Sponsor

Trials

3

Recruited

60+

Published Research Related to This Trial

In the neoMONARCH study, postmenopausal women with HR+/HER2- breast cancer showed significant decreases in Ki67 expression and achieved higher rates of complete cell-cycle arrest when treated with abemaciclib alone or in combination with anastrozole compared to anastrozole alone.

The combination therapy not only inhibited cancer cell growth but also enhanced immune activation, suggesting a dual mechanism of action that could improve treatment outcomes, while the most common side effects were manageable gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. Hurvitz, SA., Martin, M., Press, MF., et al.[2023]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Letrozole can be safely administered alongside radiotherapy in postmenopausal women with early-stage breast cancer, with no significant increase in severe skin-related toxic effects observed between concurrent and sequential treatment groups during the study.

Both treatment groups experienced similar rates of acute skin toxicity, with dermatitis being the most common issue, indicating that combining letrozole with radiotherapy does not exacerbate skin side effects significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial. Azria, D., Belkacemi, Y., Romieu, G., et al.[2022]

In a phase II study involving 16 postmenopausal women with locally advanced or metastatic HR+/HER2- breast cancer, the combination of bosutinib and letrozole showed significant treatment-related adverse events, with 15 out of 16 participants experiencing side effects, primarily diarrhea and liver enzyme elevations.

Due to a high incidence of dose-limiting toxicities and an unfavorable risk-benefit ratio, the study concluded that further investigation of bosutinib plus letrozole as a treatment option was not warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosutinib in combination with the aromatase inhibitor letrozole: a phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Moy, B., Neven, P., Lebrun, F., et al.[2021]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

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