Ribociclib + Hormone Therapy for Breast Cancer

(Adjuvant WIDER Trial)

Recruiting at 8 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Endocrine therapy

Must not be taking: Antineoplastic therapy

Disqualifiers: Metastases, Heart disease, Pregnancy, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

1400 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this open-label, multicenter, phase IIIb, single-arm study is to characterize the efficacy and safety of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a close to clinical practice patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, IIB, and a subset of Stage IIA Early Breast Cancer (EBC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can continue using standard endocrine therapy (hormone treatment) like tamoxifen or toremifene. It's best to discuss your specific medications with the trial team.

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

Research from the MONALEESA-2 trial shows that adding Ribociclib to Letrozole significantly improved the time patients lived without their cancer getting worse compared to Letrozole alone in women with advanced breast cancer. ^{1 2 3 4 5}

Is Ribociclib with hormone therapy safe for breast cancer treatment?

Ribociclib, when combined with hormone therapy like letrozole, has been shown to have a manageable safety profile in treating advanced breast cancer. Common side effects include low white blood cell counts, nausea, tiredness, diarrhea, hair loss, vomiting, constipation, headache, and back pain. ^{1 3 4 6 7}

What makes the drug Ribociclib combined with hormone therapy unique for breast cancer treatment?

Ribociclib, when combined with hormone therapy like letrozole, is unique because it significantly improves progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer, compared to hormone therapy alone. This combination targets specific proteins (CDK 4/6) that help cancer cells grow, offering a novel approach to slowing down the disease. ^{1 4 5 8 9}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults over 18 with HR-positive, HER2-negative early breast cancer that's been surgically removed and has no tumor at the margins. They should have started hormone therapy within the last 24 months and must continue it for at least another 3 years. Good performance status (able to carry out daily activities) and proper organ function are required.

Inclusion Criteria

My cancer was surgically removed with clear margins and is stage II or III.

My bone marrow and organs are functioning well.

I can take care of myself and am up and about more than half of my waking hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy for 36 months

36 months

Monthly visits for ribociclib administration

Safety Follow-up

Safety follow-up call conducted 30 days after the last dose of study treatment

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment until death, withdrawal of consent, lost to follow-up, or 48 months after the last participant's first dose

Up to 48 months

Treatment Details

Interventions

• Anastrozole
• Goserelin
• Letrozole
• Leuprolide
• Ribociclib

Trial Overview The trial is testing Ribociclib combined with standard endocrine therapies like Anastrozole, Letrozole, Leuprolide, Goserelin or Exemestane in patients with certain stages of early breast cancer. It aims to see if this combination improves survival without invasive breast cancer returning.

Participant Groups

Group I: Ribociclib + endocrine therapy Experimental Treatment 6 Interventions

Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used)

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In the MONALEESA-7 trial involving 672 premenopausal women with advanced HR-positive breast cancer, ribociclib combined with endocrine therapy significantly improved progression-free survival (23.8 months) compared to placebo (13.0 months), indicating its efficacy as a first-line treatment option.

The safety profile of ribociclib was manageable, with common grade 3 or 4 adverse events like neutropenia occurring in 61% of patients, but no treatment-related deaths were reported, suggesting that while there are risks, the benefits may outweigh them for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Tripathy, D., Im, SA., Colleoni, M., et al.[2022]

In the phase 3 MONALEESA-2 study involving 668 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of ribociclib (RIB) and letrozole (LET) significantly improved the duration of response (DoR) to 26.7 months compared to 18.6 months with placebo plus LET.

Patients receiving RIB also experienced greater tumor shrinkage and pain reduction, with 32% showing a significant tumor response at 8 weeks, reinforcing the efficacy of RIB plus LET as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Janni, W., Alba, E., Bachelot, T., et al.[2019]

In the MONALEESA-2 study involving 213 US patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole significantly improved progression-free survival (PFS) to 27.6 months compared to 15.0 months with letrozole alone, indicating its efficacy as a first-line treatment.

The most common side effects of ribociclib included neutropenia (72%), nausea (69%), and fatigue (60%), highlighting the importance of monitoring for these adverse events during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. Yardley, DA., Hart, L., Favret, A., et al.[2020]

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 the MONALEESA-2 study involving 668 postmenopausal women with advanced breast cancer, ribociclib combined with letrozole significantly improved progression-free survival (PFS) to 25.3 months compared to 16.0 months for placebo plus letrozole, demonstrating a strong treatment benefit.

The safety profile of ribociclib plus letrozole remained manageable over an extended follow-up period, with no new toxicities reported, indicating that this combination therapy is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Hortobagyi, GN., Stemmer, SM., Burris, HA., et al.[2022]

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, significantly improves median progression-free survival (PFS) in women with HR+/HER2- metastatic breast cancer when used in combination with endocrine therapy, with PFS ranging from 8 to 13 months across three phase III trials.

The treatment is well tolerated, particularly in elderly patients, and while it has some dose-limiting toxicities like neutropenia and QTc prolongation, it maintains health-related quality of life and reduces pain scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. Rascon, K., Flajc, G., De Angelis, C., et al.[2020]

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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. [2019]

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

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. [2020]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. [2022]

6. 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]

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

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. [2020]

8. 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]

9. 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]