Pre-op Radiation + Abemaciclib + Letrozole for Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Mridula George, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination of Abemaciclib and Letrozole for breast cancer?

Research shows that Abemaciclib, when combined with Letrozole, significantly improves progression-free survival in patients with advanced ER-positive, HER2-negative breast cancer. Additionally, Abemaciclib with endocrine therapy reduces the risk of recurrence in early breast cancer with a high risk of recurrence.

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Is the combination of Abemaciclib and Letrozole safe for breast cancer treatment?

Abemaciclib, when combined with endocrine therapy like Letrozole, has been shown to have an acceptable and manageable safety profile in breast cancer treatment, with common side effects including diarrhea, infections, and low white blood cell counts.

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How is the drug combination of Abemaciclib and Letrozole unique for breast cancer treatment?

This drug combination is unique because it combines Abemaciclib, a CDK4/6 inhibitor that helps stop cancer cell growth, with Letrozole, an endocrine therapy that reduces estrogen levels, potentially enhancing the effectiveness of pre-operative radiation in treating hormone receptor-positive, HER2-negative breast cancer.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Rutgers Cancer Institute of New Jersey New Brunswick, NJ

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey Lead Sponsor

Mridula George, MD Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019] Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.

2. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023] Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.

3. England 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. [2022] Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.

4. United States 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. [2023] neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.

5. Netherlands 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. [2022] Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2- advanced breast cancer patients in the Phase 3 studies MONARCH 2 (fulvestrant as ET) and MONARCH 3 (letrozole or anastrozole as ET). Here, we report age-specific safety and efficacy outcomes.

6. England 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. [2021] Endocrine therapy resistance in hormone receptor-positive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. METHODS; Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy.