Ribociclib vs. Palbociclib for Breast Cancer
(HARMONIA Trial)
Recruiting in Palo Alto (17 mi)
+51 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: SOLTI Breast Cancer Research Group
Must be taking: Endocrine therapy
Must not be taking: CDK4/6 inhibitors
Disqualifiers: Chemotherapy for advanced cancer, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients with HER2-E disease from approximately 95 sites worldwide.
In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a predefined sample size and the objective is only exploratory, given the suggested lack of efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is fully enrolled.
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's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Ribociclib or Palbociclib for breast cancer?
Research shows that Ribociclib and Palbociclib are effective in treating hormone receptor-positive, HER2-negative advanced breast cancer. Ribociclib has been reviewed for its safety and efficacy, while Palbociclib, when combined with fulvestrant, improved outcomes in patients with metastatic breast cancer.
12345What safety information is available for Ribociclib and Palbociclib in breast cancer treatment?
Ribociclib and Palbociclib are generally considered safe for treating certain types of breast cancer, but they can cause side effects. Common side effects include low white blood cell counts, fatigue, and nausea. These drugs have been studied in various settings, and while they are effective, patients should be monitored for these potential adverse effects.
16789How do Ribociclib and Palbociclib differ from other breast cancer drugs?
Ribociclib and Palbociclib are unique because they are oral drugs that inhibit cyclin-dependent kinases 4 and 6, which help control cell division, potentially improving survival and quality of life in patients with hormone receptor-positive, HER2-negative metastatic breast cancer. They are used in combination with endocrine therapy and have different safety and tolerability profiles compared to other similar drugs.
1371011Eligibility Criteria
This trial is for women with advanced HR+/HER2- breast cancer, specifically the HER2-E or Basal-like subtype. They must have a tumor block available for analysis, measurable disease by RECIST v1.1 standards, good blood and organ function, an ECOG status of 0 to 1, and be able to follow the trial procedures. Women who can become pregnant must use effective contraception and not have used CDK4/6 inhibitors or chemotherapy for advanced cancer before.Inclusion Criteria
Women who could become pregnant need to have a negative pregnancy test within a week before starting the study.
My breast cancer is either HER2-E or Basal-like subtype.
I can carry out all my daily activities without help.
+8 more
Exclusion Criteria
I have been treated with CDK4/6 inhibitors before.
I have had chemotherapy for advanced breast cancer before.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either ribociclib or palbociclib in combination with endocrine therapy (letrozole or fulvestrant) to assess progression-free survival
Up to 62 months
Follow-up
Participants are monitored for safety, adverse events, and overall survival after treatment
Up to 62 months
Exploratory Cohort
An exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab
Participant Groups
The HARMONIA study is testing whether Ribociclib combined with endocrine therapy (Letrozole or Fulvestrant) works better than Palbociclib with the same endocrine therapy in extending progression-free survival in patients with advanced breast cancer within the HER2-E subtype. It's an open-label phase III trial enrolling about 456 patients worldwide.
3Treatment groups
Experimental Treatment
Group I: Ribociclib + Endocrine TherapyExperimental Treatment1 Intervention
Ribociclib + Fulvestrant or Letrozole
Group II: Palbociclib + Endocrine TherapyExperimental Treatment1 Intervention
Palbociclib + Fulvestrant or Letrozole
Group III: Paclitaxel +/- Tislelizumab - Exploratory cohortExperimental Treatment1 Intervention
Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Palbociclib is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Ibrance for:
- HR-positive, HER2-negative advanced or metastatic breast cancer
🇪🇺 Approved in European Union as Ibrance for:
- HR-positive, HER2-negative locally advanced or metastatic breast cancer
🇨🇦 Approved in Canada as Ibrance for:
- HR-positive, HER2-negative advanced or metastatic breast cancer
🇯🇵 Approved in Japan as Ibrance for:
- HR-positive, HER2-negative advanced or recurrent breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Carle Cancer CenterUrbana, IL
Legacy Good Samaritan Hospital and Medical CentePortland, OR
Baptist Memorial Health CareOxford, MS
Bon Secours Memorial Regional Medical CenterMechanicsville, VA
More Trial Locations
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Who Is Running the Clinical Trial?
SOLTI Breast Cancer Research GroupLead Sponsor
NovartisIndustry Sponsor
Alliance Foundation Trials, LLC.Collaborator
References
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.
Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. [2022]The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit.
A Phase II Single-arm Study of Palbociclib in Patients With HER2-positive Breast Cancer With Brain Metastases and Analysis of ctDNA in Patients With Active Brain Metastases. [2023]Palbociclib is highly efficacious and well tolerated in hormone-receptor positive (HR+) metastatic breast cancer (BC) but its activity for HER2+ BC with brain metastases (BM) is unknown.
Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial. [2021]To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC).
Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. [2022]To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib).
Comparison of treatment-related adverse events of different Cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer: A network meta-analysis. [2020]Palbociclib, ribociclib and abemaciclib have all been approved in combination with endocrine therapy in hormone-receptor positive, HER2 negative metastatic breast cancer. While the efficacy of these drugs appears similar, differences in safety and tolerability are apparent.
PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study. [2023]In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated.
Palbociclib: first global approval. [2018]Palbociclib (Ibrance®) is an oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) 4 and CDK6 developed by Pfizer for the treatment of cancer. CDKs are important modulators of cell cycle entry and progression in response to growth signals, and inhibition of these kinases with palbociclib could enhance the activity of other anticancer drugs in tolerable regimens. Palbociclib, in combination with letrozole, was recently approved in the US for the first-line treatment of advanced breast cancer. Phase III development is underway worldwide investigating its use as first-line treatment in advanced breast cancer, as well as treatment of recurrent or advanced breast cancer and high-risk, early-stage breast cancer. A phase II trial is underway in the USA for non-small cell lung cancer under a US National Cancer Institute-funded research collaboration, and several phase I and II investigations are being conducted for various other solid tumour types and haematological malignancies. This article summarizes the milestones in the development of palbociclib leading to this first approval for use in postmenopausal women with estrogen-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
Cost-utility analysis of Palbociclib + letrozole and ribociclib + letrozole versus Letrozole monotherapy in the first-line treatment of metastatic breast cancer in Iran using partitioned survival model. [2023]Palbociclib and Ribociclib are cyclin-dependent kinase 4/6 oral molecular inhibitors that have the potential to improve overall survival (OS), progression-free survival (PFS), and quality of life in patients with metastatic breast cancer (MBC). The objective of this study was to analyze the cost-utility of Palbociclib and Ribociclib in comparison with Letrozole monotherapy as the first-line treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) MBC patients in Iran.
Matching-adjusted indirect treatment comparison of ribociclib and palbociclib in HR+, HER2- advanced breast cancer. [2022]Ribociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC.