Continued Access to Ribociclib for Solid Cancers

Recruiting at 3 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Ribociclib

Disqualifiers: Discontinued ribociclib, 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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 5 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing ribociclib, a drug that may help treat solid cancers. The goal is to enable patients who benefited from this treatment in a previous study to continue using it, either alone or with other experimental drugs. It suits those currently in a Novartis-sponsored study who have improved with ribociclib. Participants must not have been permanently removed from ribociclib in their previous study. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems focused on continuing ribociclib treatment for those already benefiting from it.

Is there any evidence suggesting that ribociclib (LEE011) is likely to be safe for humans?

Research has shown that ribociclib has been tested for safety in people with various types of cancer. Earlier studies identified common side effects, such as low white blood cell counts affecting many patients, and some liver issues. Specifically, a small number of patients reported liver problems, with a few cases being serious.

The FDA has already approved ribociclib for treating certain breast cancers, indicating a well-known safety profile. Doctors understand its effects on the body. While it can cause side effects, healthcare providers usually monitor and manage these, making ribociclib a well-recognized option in cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Ribociclib is unique because it targets specific proteins called cyclin-dependent kinases 4 and 6 (CDK4/6), which play a crucial role in cell division and cancer growth. Unlike traditional chemotherapy that attacks all rapidly dividing cells, ribociclib focuses on stopping cancer cells from multiplying, which can lead to fewer side effects. Researchers are excited about ribociclib because it offers a more targeted approach to treating solid tumors, potentially improving outcomes and quality of life for patients.

What is the effectiveness track record for Ribociclib in treating solid cancers?

Studies have shown that ribociclib, a type of targeted therapy, can effectively treat certain cancers by blocking proteins called CDK4 and CDK6, which help cancer cells grow. Research indicates that ribociclib, especially when combined with other cancer treatments, can slow the growth of advanced solid tumors, such as breast cancer. For example, in a study with breast cancer patients, those who received ribociclib along with another drug had better results than those who did not receive ribociclib. Overall, ribociclib is generally safe and shows promise for treating various cancers. In this trial, all participants will receive ribociclib in combination with other treatments. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for patients already participating in a Novartis-sponsored study using ribociclib (LEE011) alone or with other experimental treatments. They must be seeing positive results as judged by their doctor, and meet the original study's ongoing criteria.

Inclusion Criteria

I am currently in a Novartis study and taking ribociclib alone or with other treatments.

Patient is currently deriving clinical benefit from the study treatment, as determined by the investigator

Exclusion Criteria

I was taken off ribociclib treatment for any reason.

Patients who do not meet parent protocol criteria to continue study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Continued use of ribociclib (LEE011) as a single agent or in combination with other investigational treatments

up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive ribociclib (LEE011) as long as they benefit from the treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ribociclib (LEE011)

Trial Overview

The trial provides continued access to ribociclib (LEE011), either on its own or combined with other investigational drugs, for those who have benefited from it in previous Novartis studies that are now complete or stopped.

How Is the Trial Designed?

Group I: LEE011 Experimental Treatment 1 Intervention

All patients in all combinations with LEE011 will be entered in one arm.

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 involving patients with advanced solid tumors, the combination of sunitinib at 37.5 mg per day and irinotecan showed some antitumor activity, with 3 out of 10 patients responding, but it also caused significant side effects like neutropenia and sepsis.

The lower dose of sunitinib at 25 mg per day was better tolerated with no dose-limiting toxicities, but it did not demonstrate any antitumor activity, leading to the conclusion that this combination therapy will not be further investigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. Boven, E., Massard, C., Armand, JP., et al.[2021]

In a study involving 20 children and young adults with recurrent/refractory cancers, the combination of the WEE1 inhibitor adavosertib and carboplatin showed significant hematologic toxicity, including prolonged neutropenia and thrombocytopenia, leading to dose adjustments.

Despite the toxicity, the treatment demonstrated some efficacy, with an overall response rate of 11%, particularly in patients with specific molecular alterations related to DNA repair and replication stress, suggesting potential biomarkers for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of the WEE1 inhibitor adavosertib (AZD1775) in combination with carboplatin in children with advanced malignancies: Arm C of the AcSé-ESMART trial. Gatz, SA., Harttrampf, AC., Brard, C., et al.[2023]

In a study of 48 chemotherapy-naive men with metastatic castration-resistant prostate cancer (CRPC), dasatinib 100 mg once daily showed a favorable safety profile, with only 13% experiencing severe drug-related side effects.

The treatment demonstrated significant activity, with 44% of patients showing no disease progression at 12 weeks and notable reductions in bone turnover markers, suggesting it maintains efficacy similar to higher dosing schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer. Yu, EY., Massard, C., Gross, ME., et al.[2021]

The combination of ribociclib (LEE011) and irinotecan (SN38) showed a synergistic effect in inhibiting the growth of HT-29 colorectal cancer cells, which have a specific mutation, while it had an antagonistic effect on SW480 cells with a different mutation, indicating that the effectiveness of this combination therapy can vary based on the genetic profile of the cancer cells.

LEE011 was found to induce G1 cell cycle arrest by inhibiting retinoblastoma protein (Rb) phosphorylation, which contributed to its enhanced antiproliferative effect when combined with SN38 in HT-29 cells, highlighting the importance of understanding the molecular mechanisms behind drug interactions in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic and Antagonistic Antiproliferative Effects of Ribociclib (Lee011) and Irinotecan (SN38) on Colorectal Cancer Cells. Huang, CI., Huang, YK., Lee, HM., et al.[2023]

Bosutinib, a Src/Abl kinase inhibitor, was generally well tolerated in patients with advanced solid tumors, with the recommended phase II dose (RP2D) established at 400 mg/day due to gastrointestinal toxicities observed at higher doses.

While some patients experienced partial or complete responses, the primary efficacy endpoints for progression-free and overall survival were not met, indicating that further studies, particularly in combination therapies, are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of bosutinib, a src/abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors. Daud, AI., Krishnamurthi, SS., Saleh, MN., et al.[2014]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5727901/

Ribociclib (LEE011): mechanism of action and clinical impact ...

Based on the available data, ribociclib has a manageable tolerability profile and therapeutic potential for a variety of cancer types. Its high selectivity ...

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aacrjournals.org

aacrjournals.org/clincancerres/article/22/23/5696/122160/A-Phase-I-Study-of-the-Cyclin-Dependent-Kinase-4-6

A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor ...

The findings from this study show that single-agent ribociclib had an acceptable safety profile in patients with advanced solid tumors or lymphomas, with the ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01237236

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The primary purpose of this study is to find the highest dose of LEE011 that can be safely given to adult patients with advanced solid tumors or lymphomas for ...

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kisqali-hcp.com

kisqali-hcp.com/metastatic-breast-cancer/pk-pd-data

PK/PD Data | mBC

Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors.

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa1609709

Ribociclib as First-Line Therapy for HR-Positive, Advanced ...

We evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women.

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/209092s013,209935s021lbl.pdf

KISQALI® (ribociclib) tablets, for oral use - accessdata.fda.gov

In this pooled safety population, the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were leukocytes decreased (95%), neutrophils.

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novartis.com

novartis.com/us-en/sites/novartis_us/files/kisqali.pdf

Highlights of Prescribing Information

In patients with early breast cancer (NATALEE) treated with KISQALI, drug-induced liver injury was reported in 9 patients. (0.4%), of which 5 were Grade ≥ 3, ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2018/209092s001lbl.pdf

KISQALI® (ribociclib) tablets, for oral use - accessdata.fda.gov

The safety data reported below are based on MONALEESA-2, a clinical study ... Solid Tumors (RECIST) v1.1. Patients enrolled in MONALEESA-2 had a median ...

9.

medkoo.com

medkoo.com/products/13047

LEE011 Succinate | CAS#1374639-75-4 | 1211441-98-3

In xenograft models, Ribociclib significantly reduced tumor growth without causing substantial toxicity. These findings support its development as a targeted ...

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oncologynewscentral.com

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Ribociclib Oral

Ribociclib is used for the treatment of adults with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer in combination with an ...