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.
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.
Brief Title
Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Breast Cancer
Eligibility 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
* 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
Inclusion Criteria
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).
* 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).
Gender
All
Gender Based
false
Keywords
PAM50
intrinsic subtype
HER2-Enriched
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05207709
Org Class
Other
Org Full Name
SOLTI Breast Cancer Research Group
Org Study Id
SOLTI-2101
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase III, Multicenter, Open-label Study of Ribociclib vs. Palbociclib in Patients With Advanced Hormone Receptor-positive/HER2-negative/HER2-Enriched Breast Cancer - HARMONIA Trial
Primary Outcomes
Outcome Description
using RECIST 1.1 criteria, as assessed by local radiologists/investigators
Outcome Measure
Progression-free survival
Outcome Time Frame
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
Secondary Ids
Secondary Id
2021-002027-38
Secondary Id
LEE011A2303R
Secondary Id
AFT-58
Secondary Outcomes
Outcome Description
defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first
Outcome Time Frame
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
Outcome Measure
Progression-free survival 2
Outcome Description
the proportion of exitus patients
Outcome Time Frame
until patient death, assessed up to approximately 62 months after the first patient enrolled
Outcome Measure
Overall Survival
Outcome Description
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.
Outcome Time Frame
until disease progression or 24 weeks from treatment start.
Outcome Measure
Overall response and clinical benefit
Outcome Description
defined per RECIST 1.1
Outcome Time Frame
time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled
Outcome Measure
Time to response and duration of response
Outcome Description
Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions
Outcome Time Frame
from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled
Outcome Measure
Adverse events (safety)
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18