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

Trial Summary

What is the purpose of this trial?

This is a Phase II Trial to assess the impact of omitting adjuvant chemotherapy based on patient's selection on treatment persistence of CDK4/6 inhibitor, ribociclib (Kisqali), in a well-defined subgroup of patients with resected estrogen receptor (ER)-positive, HER2-negative, lymph node-positive breast cancer, but whose tumor profiling indicates a less aggressive biological nature (OncotypeDx 21-gene recurrence score RS 0-25).

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.

What data supports the effectiveness of the drug Ribociclib for breast cancer?

Ribociclib, when combined with letrozole, has been shown to significantly improve progression-free survival in patients with advanced hormone receptor-positive, HER2-negative breast cancer, according to the MONALEESA-2 trial. This combination is approved for use and has demonstrated benefits in various patient subgroups, including those with different types of disease progression. ^{1 2 3 4 5}

Is ribociclib safe for humans?

Ribociclib has been shown to have a manageable safety profile in clinical trials for breast cancer, with common side effects including neutropenia (low white blood cell count), nausea, and fatigue. These side effects are generally manageable with monitoring and dose adjustments. ^{1 3 6 7 8}

How is the drug Ribociclib unique in treating breast cancer?

Ribociclib is unique because it is an oral drug that specifically targets and inhibits cyclin-dependent kinases 4 and 6, which are proteins involved in cell division. This action helps to stop cancer cells from growing, and when combined with an aromatase inhibitor, it significantly improves the time patients live without their cancer getting worse compared to standard treatments. ^{1 2 3 4 9}

Research Team

Jing Du

Principal Investigator

Yale University

Eligibility Criteria

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.

My breast cancer recurrence score is 25 or lower.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

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, 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 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]

References

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

Ribociclib: First Global Approval. [2018]

2. England 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. [2019]

3. France 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. [2022]

4. 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]

5. United States 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. [2023]

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

FDA Approval Summary: Ribociclib Indicated for Male Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2019]

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

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