Ribociclib Combination Therapy for Breast Cancer

Not currently recruiting at 100 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Ribociclib

Disqualifiers: Unresolved toxicities, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of combining ribociclib, a cancer treatment drug, with other drugs for breast cancer treatment. It targets individuals already participating in a global study with Novartis who have taken ribociclib for at least six cycles with positive results. Participants must not have experienced any serious side effects that halted their ribociclib treatment and must lack local access to the drug through other means. Those benefiting from ribociclib and meeting these criteria might find this trial suitable. As a Phase 4 trial, this research aims to understand how an FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves continuing ribociclib treatment from a previous study, you may need to stay on this medication.

What is the safety track record for these treatments?

Research shows that ribociclib, when combined with other medications, is generally safe and well-tolerated. Adjusting the dose can manage most side effects, allowing patients to continue treatment. Studies on advanced breast cancer indicate that ribociclib is effective and safe for people of all ages. Many breast cancer patients have used it successfully, demonstrating its effectiveness while keeping side effects under control. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Ribociclib is unique because it targets specific proteins known as CDK4/6, which are crucial for cancer cell division and growth. Unlike traditional hormonal treatments for breast cancer, which primarily focus on blocking estrogen, Ribociclib works by inhibiting these proteins, potentially stopping cancer cells from multiplying. Researchers are excited about Ribociclib because it offers a more targeted approach that could enhance the effectiveness of existing hormone therapies like Anastrozole and Letrozole, offering new hope for improved outcomes in breast cancer treatment.

What is the effectiveness track record for ribociclib combination therapy in treating breast cancer?

Research shows that ribociclib, administered to all participants in this trial alongside other treatments, effectively treats certain types of breast cancer. Studies have found that ribociclib, when combined with hormone therapy, significantly extends the time patients live without cancer progression. Specifically, trials demonstrated a 28% reduction in the risk of cancer returning in patients with early breast cancer. This combination also helps patients with metastatic breast cancer (cancer that has spread) live longer. These findings support ribociclib as a promising treatment for those with hormone receptor-positive, HER2-negative breast cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for breast cancer patients already in a Novartis study, who've seen benefits from Ribociclib and other drugs. They must have completed at least 6 cycles of treatment with Ribociclib. Those permanently off Ribociclib or with unresolved toxicities from it can't join.

Inclusion Criteria

Currently participating in a Novartis sponsored global study (parent study), receiving treatment with ribociclib in combination with other drugs, and the parent study has fulfilled its primary objective(s)

I have been treated with ribociclib for at least 6 cycles.

You are currently benefiting from the treatment according to the doctor.

Exclusion Criteria

I had to stop taking ribociclib due to side effects that haven't gone away.

I was permanently taken off ribociclib in a previous study.

I can get and afford ribociclib where I live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue receiving ribociclib in combination with other drugs as in the parent study

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Fulvestrant
• Goserelin
• Letrozole
• Ribociclib
• Tamoxifen

Trial Overview The study tests the long-term safety of continued use of Ribociclib combined with Letrozole, Anastrozole, Goserelin, Tamoxifen, or Fulvestrant in those benefiting from it after completing primary objectives in an earlier Novartis trial.

How Is the Trial Designed?

Group I: Ribociclib Experimental Treatment 6 Interventions

All participants will receive ribociclib in combination with other drugs at the same dose/schedule as in the parent study.

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

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 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]

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]

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 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 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 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]

Citations

1. novartis.com novartis.com/us-en/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% ... Novartis Kisqali® 5-year NATALEE data demonstrate 28% reduction in risk of recurrence in the broadest early breast cancer patient population.

2. us.kisqali.com us.kisqali.com/metastatic-breast-cancer/proven-results/results-with-kisqali

Clinical Trial Results | mBC Review clinical trial results in women living with HR+, HER2- metastatic breast cancer who were treated with KISQALI. See full Prescribing and Safety Info.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12464853/

Ribociclib Plus Endocrine Therapy in Hormone Receptor ... Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) ...

4. kisqali-hcp.com kisqali-hcp.com/metastatic-breast-cancer/efficacy/efficacy-across-trials

Efficacy Across Trials | mBC KISQALI + AI or fulvestrant is proven to help a broad range of patients with HR+/HER2- mBC live longer—and that means more time doing what they love.

5. 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 ...

6. kisqali-hcp.com kisqali-hcp.com/early-breast-cancer/safety

Safety | eBC | KISQALI® (ribociclib) With KISQALI, most adverse reactions were manageable and reversible with dose reduction, which may have helped patients remain on therapy.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39826197/

advanced breast cancer treated with ribociclib plus ... Conclusions: This analysis demonstrated that ribociclib+ET is an effective and well-tolerated treatment for patients of all age groups with HR+ /HER2 - ABC, ...

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

Ribociclib Plus Endocrine Therapy in Hormone Receptor ... Importance Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival ...