Trial Summary
What is the purpose of this trial?This is an open-label, multi-center, phase I study designed to assess the maximum tolerated dose of ribociclib and belinostat in combination. The trial will open with a dose escalation followed by an expansion cohort at the identified dose. Dose escalation will be open to the enrollment of patients diagnosed with triple-negative breast cancer or ovarian cancer. Dose expansion will only be open to patients diagnosed with triple-negative breast cancer.
What safety data is available for Ribociclib and Belinostat in breast cancer treatment?The safety data for Ribociclib, also known as Kisqali, has been extensively studied in various clinical trials for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Common adverse reactions include neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. Ribociclib can also cause liver function test abnormalities and QTc prolongation, which may require caution in patients with cardiac issues. However, there is no specific safety data available for the combination of Ribociclib and Belinostat in breast cancer treatment from the provided research.23789
Is the drug Ribociclib a promising treatment for breast cancer?Yes, Ribociclib is a promising drug for breast cancer. It has been shown to improve survival rates and outcomes in patients with advanced breast cancer when used with other therapies. It is effective for a wide range of patients and has been approved by the FDA for use in combination with other treatments.13678
What data supports the idea that Ribociclib + Belinostat for Breast Cancer is an effective treatment?The available research shows that Ribociclib, when combined with other drugs like letrozole or fulvestrant, is effective for treating advanced breast cancer. Studies like the MONALEESA-2 trial found that Ribociclib with letrozole significantly improved the time patients lived without the cancer getting worse compared to letrozole alone. This suggests that Ribociclib is a promising option for patients with advanced breast cancer, although specific data on Ribociclib combined with Belinostat is not provided.34578
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications, but certain medications and supplements must be stopped at least 7 days before starting the study. These include medications that inhibit UGT1A1, herbal supplements, and medications with a known risk of inducing Torsades de Pointes. Additionally, strong and moderate inducers or inhibitors of CYP3A4/5 must be stopped 7 days prior. Consult with the trial team for specific guidance on your medications.
Eligibility Criteria
This trial is for adults with metastatic triple-negative breast cancer or recurrent ovarian cancer. Participants must have good organ function, be able to swallow pills, and not be pregnant. They should agree to use birth control and provide consent. People with certain heart conditions, unresolved diarrhea, active infections, or those who've had recent major treatments are excluded.Inclusion Criteria
I can take care of myself but might not be able to do heavy physical work.
I agree to have up to 3 biopsies on areas where my cancer has spread.
I am 18 years old or older.
I can swallow pills.
Exclusion Criteria
I am not allergic to belinostat, ribociclib, or their components.
I am not using herbal supplements or they are approved by the study lead.
I haven't had major surgery or cancer treatment in the last 4 weeks.
I am not taking any strong medication that affects liver enzymes or blood thinners like warfarin.
I do not have uncontrolled heart rhythm problems, heart failure, or chest pain.
I do not have serious heart rhythm problems or a long QT syndrome.
I have ongoing moderate to severe diarrhea.
My heart's pumping ability is below normal.
I have used CDK 4/6 or HDAC inhibitors for my cancer.
I am currently on medication for an infection.
I am currently taking medication that affects UGT1A1.
I am not taking medication known to cause heart rhythm problems.
Treatment Details
The study tests the combination of two drugs: Ribociclib and Belinostat. It's designed to find the highest dose patients can tolerate without severe side effects. The trial has two parts: first finding the right dose (dose escalation) and then giving that dose to more people (dose expansion).
1Treatment groups
Experimental Treatment
Group I: Treatment: all patientsExperimental Treatment2 Interventions
Ribociclib and belinostat will be given at escalating doses and on multiple administration schedules throughout the dose escalation component of the study. The MTD identified in the dose escalation component will be used to define the dose and administration schedule used in the dose expansion.
Belinostat is already approved in United States for the following indications:
🇺🇸 Approved in United States as Beleodaq for:
- Peripheral T-cell lymphoma (PTCL)
Find a clinic near you
Research locations nearbySelect from list below to view details:
Huntsman Cancer InstituteSalt Lake City, UT
Inova Schar Cancer InstituteFairfax, VA
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Who is running the clinical trial?
University of UtahLead Sponsor
Acrotech BiopharmaCollaborator
NovartisIndustry Sponsor
References
Ribociclib Lengthens Breast Cancer Survival. [2018]The combination of antiestrogen therapy and ribociclib, an investigational CDK4/6 inhibitor, led to improved outcomes in women with metastatic HR-positive, HER2-negative breast cancer, according to findings presented at a meeting of the European Society for Medical Oncology. The combination significantly increased progression-free survival compared with letrozole alone in a large phase III trial-data that could lead to FDA approval.
FDA Approval: Ribociclib for the Treatment of Postmenopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. [2019]On March 13, 2017, the FDA approved ribociclib (KISQALI; Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2). A total of 668 patients were randomized to receive either ribociclib plus letrozole (n = 334) or placebo plus letrozole (n = 334). An improvement in progression-free survival (PFS) was observed in patients receiving ribociclib plus letrozole compared with patients receiving placebo plus letrozole [HR = 0.556; 95% confidence interval (CI), 0.429-0.720]. Overall response rate (ORR) in patients with measurable disease was 52.7% (95% CI, 46.6-58.9) in the ribociclib plus letrozole arm and 37.1% (95% CI, 31.1-43.2) in the placebo plus letrozole arm. Overall survival data were immature. The most common adverse reactions observed in 20% or more of patients taking ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. This article summarizes FDA decision-making and data supporting the approval of ribociclib. Clin Cancer Res; 24(13); 2999-3004. ©2018 AACRSee related commentary by Spring and Bardia, p. 2981.
Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. [2020]To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of ribociclib (LEE011, Kisqali) in hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer.
Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. [2020]Label="BACKGROUND">In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR+/HER2- advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2.
Resistance Mechanisms to CDK Inhibition plus Endocrine Therapy Identified. [2022]In early-stage breast cancer, ribociclib plus letrozole led to estrogen-independent resistance pathways.
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]Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months).
Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection. [2022]Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib's efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients' prognoses.
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]Ribociclib plus letrozole demonstrated manageable safety and efficacy profiles in hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) in the Phase 3b CompLEEment-1 trial.
FDA Approval Summary: Ribociclib Indicated for Male Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. [2023]On December 10, 2021, the FDA expanded the indications for ribociclib to include male patients for the treatment of hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. Ribociclib is now indicated in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy in adult patients, or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy (ET), in postmenopausal women or in men. The efficacy of ribociclib+AI for male patients was primarily based on previous favorable benefit-risk assessments of ribociclib from MONALEESA-2 and MONALEESA-7 trials, and supported by COMPLEEMENT-1, an open-label, single arm, multicenter clinical trial, in which 39 male patients (n=3,246 total patients) received ribociclib+letrozole+goserelin/leuprolide. The ORR based on confirmed responses in male patients with measurable disease at baseline was 46.9% (95% CI: 29.1, 65.3), consistent with an ORR 43.6% (95% CI: 41.5, 45.8) in the overall population. Overall, adverse reactions occurring in male patients were similar to those occurring in female patients treated with ribociclib+ET. The efficacy of ribociclib+fulvestrant for male patients was primarily based on the previous findings of a favorable benefit-risk assessment from the MONALEESA-3 trial, supported by FDA review of clinical data of a limited number of male patients treated in clinical practice receiving ribociclib+fulvestrant. The known mechanism of action, biologic rationale, and clinical information available adequately demonstrate that the efficacy and safety of ribociclib+AI/fulvestrant are similar in male and female patients. This article summarizes the FDA's decision-making and data supporting the approval of ribociclib in male patients with breast cancer, and discusses regulatory insights.