Ribociclib and Endocrine Therapy for Breast Cancer

(SELECT Trial)

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Hormone replacement therapy

Disqualifiers: Metastases, T4 tumors, N3 tumors, 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)

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 9

Duration: 1 year

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating a specific type of breast cancer that is estrogen receptor-positive and HER2-negative. Researchers aim to determine if skipping chemotherapy and using ribociclib (a type of targeted therapy) with hormone therapy is effective for patients whose tumor profile indicates less aggressive cancer. Ideal candidates for this trial have undergone surgery for this type of breast cancer and have a tumor profile showing a low to moderate risk of recurrence. Participants must not have received chemotherapy for this cancer before. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications that interact with the trial drugs, like those affecting the QT interval or CYP3A4/5 enzymes. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that ribociclib, when combined with hormone therapy, is generally well-tolerated. Studies have demonstrated significant benefits for patients with certain types of breast cancer. For example, the NATALEE trial found that combining ribociclib with a nonsteroidal aromatase inhibitor (a type of hormone therapy) improved survival rates.

Patients in these studies reported that while side effects can occur, they are usually manageable. Some patients experienced side effects, but these were often mild to moderate. Ribociclib is already approved by the FDA for treating certain breast cancers, which supports its safety.

In summary, past studies have shown positive safety results for ribociclib, making it a promising option for patients considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Ribociclib is unique because it specifically targets cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cancer cell growth. Unlike traditional chemotherapy, which can affect both cancerous and healthy cells, ribociclib offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about the combination of ribociclib with optimized endocrine therapy because it may enhance the effectiveness of hormone therapies, which are standard for hormone receptor-positive breast cancer. Additionally, the treatment arm involving adjuvant chemotherapy followed by ribociclib and endocrine therapy represents a novel sequence that could improve outcomes by addressing cancer at multiple stages.

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

Research has shown that ribociclib, when combined with hormone therapy, improves outcomes for breast cancer patients. One study found that this combination significantly increased the rate of patients remaining free from invasive cancer compared to hormone therapy alone. After three years, 90.8% of patients using ribociclib with hormone therapy did not experience cancer recurrence. This trial will test ribociclib with optimized endocrine therapy in one arm, while another arm will include adjuvant chemotherapy followed by ribociclib and optimized endocrine therapy. For those also receiving additional chemotherapy, similar improvements in survival and disease control have been observed. These findings suggest that ribociclib, along with hormone therapy, is a promising treatment option for certain breast cancer patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Jing Du

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with moderate to high-anatomical risk, low-genomic risk, ER-positive, HER2-negative breast cancer. It's designed to see if patients can skip chemo and instead use a combination of Ribociclib and hormone therapy (Letrozole or Anastrazole) along with Goserelin.

Inclusion Criteria

My cancer stage fits specific criteria after surgery.

I have been mostly active and able to carry out all my pre-disease activities up to a month before starting the study treatment.

I can take pills by mouth.

Exclusion Criteria

Pregnancy or lactating women or women who plan to become pregnant or breast-feed during the trial

I haven't taken certain medications in the last 7 days.

My cancer has spread to nearby lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ribociclib and optimized endocrine therapy or adjuvant chemotherapy followed by ribociclib and optimized endocrine therapy

1 year

Every 3 months during the first year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months during years 2 and 3

Long-term follow-up

Participants are monitored for invasive disease-free survival and other secondary outcomes

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Ribociclib

Trial Overview The study tests whether using the drug Ribociclib alongside standard endocrine therapies like Letrozole or Anastrazole without chemotherapy can be effective in treating certain breast cancers. The goal is to improve patient quality of life by reducing treatment side effects.

How Is the Trial Designed?

Group I: Ribociclib + Optimized Endocrine Therapy Experimental Treatment 4 Interventions

Combination of ribociclib and optimized endocrine therapy

Group II: Adjuvant Chemotherapy + Ribociclib & Optimized Endocrine Therapy Experimental Treatment 5 Interventions

Adjuvant chemotherapy followed by a combination of ribociclib and optimized endocrine therapy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

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]

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 is a selective oral inhibitor of CDK 4 and 6, specifically approved for treating hormone receptor-positive breast cancer.

When combined with an aromatase inhibitor, ribociclib significantly improves progression-free survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cycling Toward Progress: Ribociclib, a CDK 4/6 Inhibitor for Breast Cancer. Spring, L., Bardia, A.[2019]

Ribociclib has been approved by the FDA for use in male patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing an overall response rate of 46.9% in a clinical trial with 39 male patients.

The safety profile of ribociclib in male patients is similar to that observed in female patients, indicating that its efficacy and safety are consistent across genders when used in combination with aromatase inhibitors or fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ribociclib Indicated for Male Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. Gao, JJ., Osgood, CL., Feng, Z., et al.[2023]

Ribociclib, approved by the FDA for treating advanced breast cancer, significantly improves progression-free survival when combined with letrozole compared to a placebo, as shown in a study of 668 patients.

The overall response rate for patients receiving ribociclib plus letrozole was 52.7%, compared to 37.1% for those on placebo, indicating its efficacy, although common side effects included neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Ribociclib for the Treatment of Postmenopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. Shah, A., Bloomquist, E., Tang, S., et al.[2019]

Ribociclib, a CDK 4/6 inhibitor, has been shown to significantly improve progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer when used in combination with letrozole, based on the results of the MONALEESA-2 phase 3 trial involving a randomized, double-blind design.

The study highlights ribociclib's effectiveness across various patient subgroups, including those with different ages and disease histories, establishing it as a valuable treatment option for managing advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib for the first-line treatment of advanced hormone receptor-positive breast cancer: a review of subgroup analyses from the MONALEESA-2 trial. Hortobagyi, GN.[2019]

In a study of 554 Italian patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole showed a clinical benefit rate of 71.7% and a median time to progression of 26.7 months, indicating effective treatment outcomes.

The treatment was associated with manageable safety profiles, with 98.9% of patients experiencing all-grade adverse events, primarily neutropenia, but health-related quality of life scores remained stable during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study. De Laurentiis, M., Caputo, R., Mazza, M., 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]

In the phase III MONALEESA-7 trial, ribociclib combined with endocrine therapy significantly improved overall survival (OS) in pre-/perimenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer, with a median OS of 58.7 months compared to 48.0 months for the placebo group.

The study included 672 patients and showed that ribociclib not only delayed the time to first chemotherapy but also had consistent OS benefits across various subgroups, including those under 40 years old, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Lu, YS., Im, SA., Colleoni, M., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40996773/

4-Year Outcomes From the NATALEE Randomized Clinical ... Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs ...

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2839158

Ribociclib Plus Endocrine Therapy in Hormone Receptor ... Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01727-2/fulltext

Adjuvant ribociclib plus nonsteroidal aromatase inhibitor ... This 5-year follow-up of efficacy outcomes from NATALEE demonstrated persistent iDFS, DDFS, DRFS, and RFS benefit over time in patients with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00144

Final Results of RIGHT Choice: Ribociclib Plus Endocrine ... First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2114663

Overall Survival with Ribociclib plus Letrozole in Advanced ... First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR- ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000061

Efficacy, safety, and patient-reported outcomes across ... Ribociclib + endocrine therapy (ET) showed significant progression-free survival (PFS) and overall survival (OS) benefits in the MONALEESA trials in ...

7. novartis.com novartis.com/news/media-releases/novartis-kisqali-5-year-natalee-data-demonstrate-28-reduction-risk-recurrence-broadest-early-breast-cancer-patient-population

Novartis Kisqali® 5-year NATALEE data demonstrate 28% ... "These five-year results show that the benefit of ribociclib persists well beyond the completion of treatment, offering these at-risk patients a ...

8. pharmacytimes.com pharmacytimes.com/view/five-year-natalee-data-show-ribociclib-improves-outcomes-in-high-risk-hr-her2-early-breast-cancer

Five-Year NATALEE Data Show Ribociclib Improves ... New data from the NATALEE trial reveals ribociclib significantly improves invasive disease-free survival in HR+/HER2– early breast cancer.