Clinical trial NCT05207709: Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Keywords: PAM50
intrinsic subtype
HER2-Enriched
Lead sponsor: SOLTI Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Novartis
name: Alliance Foundation Trials, LLC.
First posted: 2022-01-26
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free survival
timeFrame: 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 outcomes:
measure: Progression-free survival 2
timeFrame: 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
measure: Overall Survival
timeFrame: until patient death, assessed up to approximately 62 months after the first patient enrolled
measure: Overall response and clinical benefit
timeFrame: until disease progression or 24 weeks from treatment start.
measure: Time to response and duration of response
timeFrame: time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled
measure: Adverse events (safety)
timeFrame: from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Miami
country: United States
facility: Mount Sinai Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky, Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Sinai of Baltimore
state: Maryland
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Oxford
country: United States
facility: Baptist Memorial Health Care
state: Mississippi
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Londonderry
country: United States
facility: NHOH
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore
state: New York
city: New York
country: United States
facility: Nothwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Care
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Dayton Clinical Oncology
state: Ohio
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Cente
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Upstate Carolina Medical Center
state: South Carolina
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center
state: Virginia
city: Mechanicsville
country: United States
facility: Bon Secours Memorial Regional Medical Center
state: Virginia
city: Madison
country: United States
facility: Unv. Wisconsin
state: Wisconsin
city: Creixomil
country: Portugal
facility: Hospital Senhora da Oliveira - Guimarães
city: Lisboa
country: Portugal
facility: IPO Lisboa
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia
city: Badalona
country: Spain
facility: Institut Català d' Oncologia (ICO Badalona)
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia (ICO Hospitalet)
state: Barcelona
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Illes Balears
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
state: Islas Canarias
city: A Coruña
country: Spain
facility: Hospital Clínico Universitario de A Coruña
state: La Coruña
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago CHUS
state: La Coruña
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Vall d´Hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: IOB-Institute of Oncology. Hospital Quironsalud Barcelona
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Cáceres
country: Spain
facility: Complejo Hospitalario San Pedro de Alcántara
city: Girona
country: Spain
facility: Institut Català d' Oncologia de Girona (ICO Girona)
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: H. Clínico San Cecilio de Granada
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: León
country: Spain
facility: Complejo Asistencial Universitario de León
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal (CIOCC)
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital Universitario Morales Meseguer
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena
city: Sevilla
country: Spain
facility: Hospital Quiron Salud Sagrado Corazon Sevilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología (IVO)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
affiliation: Hospital Clínic of Barcelona / SOLTI
name: Aleix Prat, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Lisa A Carey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stefanie Spielman Comprehensive Breast Center
name: Dan G Stover, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínic of Barcelona / SOLTI cancer research group
name: Tomás Pascual, MD
role: PRINCIPAL_INVESTIGATOR
References: