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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of Ribociclib, a medication, when combined with postoperative radiation therapy for women with high-risk ER+ breast cancer. The researchers focus on finding a suitable dose of Ribociclib that can be safely used alongside radiation. Eligible participants have breast cancer involving multiple lymph nodes and have already undergone surgery and chemotherapy. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that Ribociclib combined with radiation therapy is likely to be safe?

Research shows that Ribociclib, when combined with radiation therapy, might be safe for treating breast cancer. Studies have found that Ribociclib is usually well-tolerated alongside other breast cancer treatments. Some patients have experienced side effects, but these are often manageable. Common side effects include fatigue and low white blood cell counts, which are usually mild.

Ribociclib is already approved for use with hormone therapy in other types of breast cancer, indicating that its safety is well-understood. This knowledge gives doctors a good understanding of its effects on the body. Although this trial is in the early stages, this background provides some reassurance about its safety. However, always discuss any concerns with a doctor, who can provide the most personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about Ribociclib combined with radiation therapy for breast cancer because it offers a novel approach by integrating a CDK4/6 inhibitor with standard radiation treatment. While typical breast cancer treatments often rely on chemotherapy and hormone therapy, Ribociclib targets specific proteins involved in cell division, potentially enhancing the effectiveness of radiation therapy. This combination might not only improve the precision of targeting cancer cells but also reduce the likelihood of cancer cell survival and replication, offering hope for more effective and lasting treatment outcomes.

What evidence suggests that Ribociclib combined with radiation therapy might be an effective treatment for breast cancer?

Research has shown that ribociclib, when combined with radiation therapy, may help treat high-risk ER+ breast cancer. In this trial, all participants will receive ribociclib alongside standard radiation therapy. Earlier studies indicate that ribociclib, a drug for certain breast cancers, can increase tumor sensitivity to radiation. Real-world studies have found that patients using ribociclib often experience longer periods without cancer progression. This suggests ribociclib might enhance the effectiveness of radiation therapy in combating cancer. Additionally, ribociclib is already approved for use with other treatments for some early-stage breast cancers, supporting its potential benefits. ^{2 4 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

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]

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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10444

Ribociclib Given Concurrently with Postoperative Radiation ... Giving ribociclib concurrently with postoperative radiation therapy may be safe and effective in treating patients with high risk, node positive, hormone ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820922001884

Real-World Outcomes of Ribociclib and Aromatase ... This real-world registry cohort had a longer median duration of treatment (24.5 vs. 20.2 months) and superior progression free survival (>36.5 vs. 25.3 months) ...

3. uhhospitals.org uhhospitals.org/for-clinicians/articles-and-news/articles/2024/12/newer-generation-breast-cancer-drugs-increase-tumors-vulnerability-to-radiation-therapy

Newer Generation Breast Cancer Drugs Increase Tumor's ... Dr. Speers and his colleagues have launched a Phase 1 clinical trial at UH Seidman Cancer Center of ribociclib administered concurrently with postoperative ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12176360/

Real-World Outcomes of Ribociclib Treatment in Patients ... Our retrospective data support the notion that ribociclib-based therapy is effective and safe in patients with HR+/HER2- ABC/MBC.

5. breastcancer.org breastcancer.org/news/kisqali-early-stage-breast-cancer

FDA Approves Kisqali for Early-Stage Breast Cancer Kisqali can now be used in combination with an aromatase inhibitor to treat stage II and stage III breast cancer after surgery.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05996107

NCT05996107 | Study of Ribociclib Administered ... The purpose of this research study is to determine the safety, tolerability and dose of Ribociclib when combined with adjuvant radiation in women with ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05996107

Study of Ribociclib Administered Concurrently With ... Safety evaluations will be based on the incidence, intensity, and type of adverse events, and clinically significant changes in the patient's physical ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9498176/

Real-World Clinical Outcomes of Ribociclib in Combination ... Our work confirms that ribociclib in combination with endocrine therapy is highly effective in the treatment of premenopausal HR+/HER2− advanced breast cancer ...