Metastatic Breast Cancer
Conditions
Keywords
PAM50, intrinsic subtype, HER2-Enriched
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.
Interventions
DRUGRibociclib + Letrozole OR Fulvestrant
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
DRUGPaclitaxel +/- Tislelizumab
Patients in this arm could receive as the first line of therapy
Sponsors
SOLTI Breast Cancer Research Group
Novartis
Alliance Foundation Trials, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Histologically documented HR-positive and HER2-negative breast cancer by local testing * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer. * Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period. * HER2-E or Basal-like subtype as per central PAM50 analysis. * Measurable disease or non-measurable disease, as defined by RECIST v1.1 * Adequate hematologic and end-organ function * Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. * Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization. * Women of CBP must be willing to use highly effective methods of contraception. * 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
Exclusion criteria
* Prior therapy with any CDK4/6 inhibitors. * Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Survival | until patient death, assessed up to approximately 62 months after the first patient enrolled | the proportion of exitus patients |
| 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. |
| 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 |
| 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 |
Countries
Portugal, Spain, United States
Contacts
PRINCIPAL_INVESTIGATORAleix Prat, MD
Hospital Clínic of Barcelona / SOLTI
PRINCIPAL_INVESTIGATORLisa A Carey, MD
UNC Lineberger Comprehensive Cancer Center
PRINCIPAL_INVESTIGATORDan G Stover, MD
Stefanie Spielman Comprehensive Breast Center
PRINCIPAL_INVESTIGATORTomás Pascual, MD
Hospital Clínic of Barcelona / SOLTI cancer research group
Outcome results
None listed