Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT05207709
- Lead Sponsor
- SOLTI Breast Cancer Research Group
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 456
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Histologically documented HR-positive and HER2-negative breast cancer by local testing
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
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Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
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HER2-E or Basal-like subtype as per central PAM50 analysis.
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Measurable disease or non-measurable disease, as defined by RECIST v1.1
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Adequate hematologic and end-organ function
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Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
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Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization.
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Women of CBP must be willing to use highly effective methods of contraception.
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Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at screening:
- QTcF interval (QT interval using Fridericia's correction) at screening < 450 msec.
- Resting heart rate 50-90 beats per minute (determined from the ECG).
Main
- Prior therapy with any CDK4/6 inhibitors.
- Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ribociclib + Endocrine Therapy Ribociclib + Letrozole OR Fulvestrant Ribociclib + Fulvestrant or Letrozole Palbociclib + Endocrine Therapy Palbociclib + Letrozole OR Fulvestrant Palbociclib + Fulvestrant or Letrozole Paclitaxel +/- Tislelizumab - Exploratory cohort Paclitaxel +/- Tislelizumab Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
- Primary Outcome Measures
Name Time Method Progression-free survival From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled using RECIST 1.1 criteria, as assessed by local radiologists/investigators
- Secondary Outcome Measures
Name Time Method Time to response and duration of response time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled defined per RECIST 1.1
Progression-free survival 2 From randomization until documented progression to second line of therapy, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first
Overall response and clinical benefit until disease progression or 24 weeks from treatment start. defined as percentage of patients with CR, PR per RECIST 1.1 or SD lasting 24 weeks or longer, as defined by RECIST 1.1.
Overall Survival until patient death, assessed up to approximately 62 months after the first patient enrolled the proportion of exitus patients
Adverse events (safety) from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions
Trial Locations
- Locations (71)
Morton Plant Hospital
🇺🇸Clearwater, Florida, United States
University of Miami
🇺🇸Coral Gables, Florida, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Mount Sinai Florida
🇺🇸Miami, Florida, United States
Northwestern
🇺🇸Chicago, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
University of Kentucky, Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Sinai of Baltimore
🇺🇸Baltimore, Maryland, United States
Dana Faber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Baptist Memorial Health Care
🇺🇸Oxford, Mississippi, United States
Scroll for more (61 remaining)Morton Plant Hospital🇺🇸Clearwater, Florida, United States