Ribociclib + Hormone Therapy for Breast Cancer

(Adjuvant WIDER Trial)

Recruiting at 160 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining ribociclib, a cancer growth blocker, with hormone therapy to improve survival in individuals with certain types of early breast cancer. The focus is on hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer. Individuals who have undergone surgery to remove their tumor and are in specific stages of breast cancer may be suitable candidates, particularly if they have previously used hormone therapy and show no signs of cancer spreading beyond nearby lymph nodes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that patients usually tolerate ribociclib well. Adjusting the dose can manage most side effects, allowing patients to continue treatment. Anastrozole is safe for long-term use and effectively reduces breast cancer risk. Letrozole also offers lasting benefits in managing breast cancer and is safe. Goserelin is well-tolerated, and studies show it works effectively for premenopausal women with few side effects. Leuprolide has proven to be a safe option for treating breast cancer in premenopausal women.

These treatments are part of the trial to evaluate their combined effectiveness. Existing research shows they are safe and effective when used alone or with other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment for breast cancer because it combines ribociclib with hormone therapy to target cancer cells more effectively. Ribociclib is a CDK4/6 inhibitor, which works by interfering with specific proteins that promote cancer cell division, offering a different mechanism compared to traditional hormone therapies like tamoxifen or aromatase inhibitors alone. This combination approach has the potential to enhance the effectiveness of hormone therapy, possibly leading to better outcomes for patients, especially those who may not respond as well to standard treatments.

What evidence suggests that the combination of ribociclib and hormone therapy could be effective for breast cancer?

This trial will evaluate the combination of ribociclib with hormone therapy for breast cancer. Research has shown that combining ribociclib with hormone therapy can significantly lower the risk of breast cancer recurrence. One study found it reduced the risk of recurrence by 28% in patients with early breast cancer. Participants in this trial will receive ribociclib alongside hormone therapies such as anastrozole, which can decrease the chance of breast cancer returning by 41% and reduce deaths from breast cancer by 34%. Letrozole has also significantly lowered breast cancer events. Goserelin and leuprolide, included in the trial, block hormones that help cancer grow. Goserelin is as effective as other doses, and leuprolide effectively reduces cancer growth in premenopausal women. Overall, using ribociclib with these hormone therapies may improve outcomes for breast cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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, 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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... The results of the Oxford meta-analyses3,4 have demonstrated significant reduction in both disease recurrence (41%) and breast cancer specific mortality (34%) ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext

Use of anastrozole for breast cancer prevention (IBIS-II) Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase ...

3. news.cancerresearchuk.org news.cancerresearchuk.org/2023/11/07/anastrozole-licensed-prevent-breast-cancer-high-risk-women/

Thousands of women offered anastrozole to help prevent ... Cases of invasive oestrogen receptor-positive breast cancer specifically were reduced by 54%, and ductal carcinoma in situ by 59%, especially in ...

4. breastcancer.org breastcancer.org/research-news/10-years-arimidex

10 Years of Arimidex Reduces Recurrence Risk ... Taking Arimidex for 10 years after breast cancer surgery reduced recurrence risk, but didn't improve overall survival.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus anastrozole in ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

7. breastcancer.org breastcancer.org/research-news/risk-reducing-effects-of-arimidex-last-years

Risk-Reducing Effects of Arimidex for High- ... The new results show that women who took Arimidex were 50% less likely to be diagnosed with breast cancer than women who didn't take Arimidex.