Ribociclib + Radiation Therapy for Breast Cancer

Recruiting at 2 trial locations

Overseen By Cancer AnswerLine

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: CYP3A4/5 inhibitors, CYP3A4/5 inducers

Disqualifiers: Pregnancy, Distant metastases, Heart disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine the safety, tolerability and dose of Ribociclib when combined with adjuvant radiation in women with high-risk ER+ breast cancer. Once enrolled on study, patients will begin treatment with Ribociclib 400 mg daily at the same time as they initiate standard of care adjuvant radiation therapy- 50 Gy in 25 fractions or 42.56 Gy in 16 fractions +/- 10 Gy boost including comprehensive nodal. Paitents will continue treatment with Ribociclib for up to 6 weeks.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, herbal supplements, and fruits that affect the enzyme CYP3A4/5 at least 7 days before starting the study. If you are on medications that prolong the QT interval, you may need to stop or replace them with safer alternatives.

What data supports the effectiveness of the treatment Ribociclib + Radiation Therapy for Breast Cancer?

Research shows that radiation therapy after surgery can help reduce the chance of breast cancer coming back in high-risk patients. Additionally, combining surgery with radiation therapy is a standard approach for early breast cancer, improving local control and survival. ^{1 2 3 4 5}

Is the combination of Ribociclib and Radiation Therapy safe for breast cancer patients?

Ribociclib, when used with radiation therapy, has shown some safety concerns, particularly with side effects like neutropenia (a drop in white blood cells), but these are generally manageable with careful monitoring and dose adjustments. While there is limited data on the combined use of Ribociclib and radiation therapy, early studies suggest that the side effects can be managed effectively. ^{6 7 8 9 10}

How does the treatment Ribociclib + Radiation Therapy for Breast Cancer differ from other treatments?

Ribociclib is a unique drug because it is a CDK4/6 inhibitor that helps stop cancer cells from growing by causing cell-cycle arrest. When combined with radiation therapy, it offers a novel approach for treating breast cancer, although its safety profile when used with radiation is still being evaluated. ^{6 7 9 11 12}

Research Team

Erin Cobain, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Corey Speers, MD, PhD

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

This trial is for women over 18 with high-risk, ER+/HER2- breast cancer who've had surgery with clear margins and completed chemotherapy. They must have good organ function, not be pregnant or breastfeeding, and can't have distant metastases or a history of CDK4/6 inhibitors. Participants need to be able to take oral medication and sign consent.

Inclusion Criteria

My breast cancer is ER/PR-positive, HER2-negative with specific lymph node involvement.

I have mostly recovered from my chemotherapy and surgery, except for possible nerve issues or hair loss.

My blood, liver, and kidney tests are within normal ranges.

Exclusion Criteria

I am not taking any other cancer treatments or experimental drugs.

My breast cancer has spread beyond the nearby lymph nodes or has come back.

My blood pressure is often above 160 mmHg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ribociclib 400 mg daily concurrently with adjuvant radiation therapy for up to 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for recurrence-free survival and overall survival

up to 2 years

Treatment Details

Interventions

• Postoperative Radiation Therapy
• Ribociclib

Trial Overview The study tests the safety and appropriate dose of Ribociclib when taken alongside standard postoperative radiation therapy in patients with certain high-risk breast cancers. The treatment includes daily Ribociclib for up to six weeks concurrent with radiation therapy.

Participant Groups

Group I: RT + Ribociclib Experimental Treatment 2 Interventions

All patients will be treated with Ribociclib and standard of care radiation therapy

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Findings from Research

In a study of 1708 high-risk premenopausal women with breast cancer, adding radiotherapy after mastectomy significantly reduced locoregional recurrences from 32% to 9% compared to chemotherapy alone.

The combination of radiotherapy and chemotherapy improved both disease-free survival (48% vs. 34%) and overall survival (54% vs. 45%) at 10 years, demonstrating the efficacy of postoperative irradiation in enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. Overgaard, M., Hansen, PS., Overgaard, J., et al.[2022]

In a study of 138 women with locally advanced or high-risk breast cancer, neoadjuvant radiation therapy (NART) resulted in a pathologic complete response (pCR) in 36.4% to 42.1% of patients, with even higher rates in HER2+ (73.8%-85.7%) and triple-negative cancers (47.6%-57.1%).

The study found that NART is feasible and leads to comparable postoperative complication rates to standard care, with excellent long-term outcomes: 98.1% locoregional recurrence-free survival, 83.6% distant metastasis-free survival, and 95.3% overall survival at 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective. Lin, YH., Chidley, P., Admojo, L., et al.[2023]

In a study of 29,270 breast cancer patients with positive lymph nodes after neoadjuvant chemotherapy, 62.5% received postmastectomy radiation therapy (PMRT), indicating significant underuse, especially among patients with advanced nodal disease (ypN2 and ypN3).

PMRT was associated with improved overall survival specifically in ypN3 patients, with a 5-year survival rate of 66% compared to 63% for those not receiving PMRT, highlighting the potential survival benefit of this treatment in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmastectomy Radiation in Breast Cancer Patients With Pathologically Positive Lymph Nodes After Neoadjuvant Chemotherapy: Usage Rates and Survival Trends. Ohri, N., Moshier, E., Ho, A., et al.[2022]

Recent advancements in radiation therapy for early breast cancer, including shorter treatment schedules and improved delivery techniques, enhance local control and reduce side effects, leading to better patient outcomes.

Future research should aim to identify molecular markers that indicate how sensitive a tumor is to radiation, which could help in developing targeted treatments that improve the effectiveness of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy (RT) after breast-conserving surgery (BCS) in 2015--The year of radiation therapy advances. Kirova, YM.[2018]

The review highlights the current standards and ongoing debates regarding the use of postoperative radiotherapy after surgery for breast cancer, particularly following neoadjuvant systemic therapy.

It emphasizes the importance of collecting detailed data on radiotherapy characteristics and outcomes in future clinical studies to better understand its effectiveness based on various clinical and biological factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Radiation Treatment Decisions for Patients Who Receive Neoadjuvant Chemotherapy. Magrini, SM., Buglione, M., Costa, L.[2015]

In a study of 16 patients with hormone-receptor positive metastatic breast cancer receiving concurrent radiotherapy and CDK4/6 inhibitors (palbociclib or ribociclib), the treatment was generally well tolerated despite a high incidence of hematological toxicity, particularly neutropenia.

Neutropenia was observed in 31.2% of patients, with 25% experiencing grade 3 and 6.3% grade 4 toxicity; notably, many patients had a history of neutropenia from previous palbociclib cycles, indicating that prior toxicity may predict future risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity. Ippolito, E., Greco, C., Silipigni, S., et al.[2020]

Ribociclib, a CDK4-6 inhibitor, has been approved as a first-line treatment for metastatic breast cancer, showing significant improvement in progression-free survival compared to endocrine therapy alone.

Preliminary data from five patients treated with ribociclib and palliative radiotherapy suggest a need for further investigation into the safety and efficacy of this combination, as ribociclib has a challenging toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer. Meattini, I., Desideri, I., Scotti, V., et al.[2022]

In a real-world study of 53 women with HR+/HER2- metastatic breast cancer treated with ribociclib, the most common adverse event was neutropenia, affecting 69.8% of patients, but these side effects were manageable with monitoring and dose adjustments.

The median progression-free survival (PFS) for patients on ribociclib was 27.3 months, and importantly, dose reductions did not correlate with disease progression, suggesting that ribociclib remains effective even with adjusted dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival? Fernández-Cuerva, C., Chinchilla-Alarcón, T., Alcaraz-Sánchez, JJ.[2023]

Ribociclib is an oral medication that inhibits CDK 4 and 6, leading to cell cycle arrest in cancer cells, and has been approved in the USA for treating advanced breast cancer in combination with an aromatase inhibitor.

The drug is currently undergoing further phase III trials for breast cancer and is being tested in early-phase trials for other types of solid tumors and blood cancers, highlighting its potential as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib: First Global Approval. Syed, YY.[2018]

CDK4/6 inhibitors (CDK4/6i) like abemaciclib and ribociclib have become the standard treatment for hormone receptor-positive, HER2-negative metastatic breast cancer, significantly improving survival outcomes when combined with endocrine therapy.

There is limited and conflicting data on the safety of combining CDK4/6i with radiation therapy, highlighting the need for further research to understand potential toxicities in both metastatic and early breast cancer settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis. Becherini, C., Visani, L., Caini, S., et al.[2023]

Ribociclib, used for treating metastatic hormone-positive breast cancer, can cause severe liver toxicity, as demonstrated in a case where a 54-year-old woman developed acute fulminant toxic hepatitis after treatment.

Despite discontinuing ribociclib, the patient's liver toxicity persisted, highlighting the need for careful monitoring and alternative treatment options, such as exemestane, in cases of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer. Topcu, A., Yasin, AI., Shbair, AT., et al.[2021]

Ribociclib, when combined with letrozole, has shown significant efficacy in treating hormone receptor positive (HR+) and HER2-negative advanced breast cancer, as evidenced by a complete clinical response in a postmenopausal patient with aggressive disease after just three months of treatment.

The treatment was well tolerated with minimal side effects, and the patient maintained a complete response for 15 months, highlighting the potential for long-lasting benefits in managing advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Clinical Response in Locally Advanced Metastatic de novo Breast Cancer after Front-Line Treatment with Ribociclib/Letrozole within the RIBANNA Study. Rudlowski, C., Beermann, N., Leitzen, L., et al.[2022]

References

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

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. [2022]

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

Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective. [2023]

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

Postmastectomy Radiation in Breast Cancer Patients With Pathologically Positive Lymph Nodes After Neoadjuvant Chemotherapy: Usage Rates and Survival Trends. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Radiation therapy (RT) after breast-conserving surgery (BCS) in 2015--The year of radiation therapy advances. [2018]

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

Optimizing Radiation Treatment Decisions for Patients Who Receive Neoadjuvant Chemotherapy. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival? [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Ribociclib: First Global Approval. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Complete Clinical Response in Locally Advanced Metastatic de novo Breast Cancer after Front-Line Treatment with Ribociclib/Letrozole within the RIBANNA Study. [2022]