Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype

Metastatic Breast Cancer Clinical Trial

— HARMONIA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05207709
• Other study ID #: SOLTI-2101
• Secondary ID: 2021-002027-38LE
• Status: Recruiting
• Phase: Phase 3
• Start date: March 28, 2022
• Est. completion date: March 1, 2027

Study information

• Verified date: June 2023
• Source: SOLTI Breast Cancer Research Group
• Contact: Juan M Ferrero-Cafiero, PharmD
• Phone: 606819182
• Email: juan.ferrero[@]gruposolti.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 456
• Est. completion date: March 1, 2027
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Ribociclib + Letrozole OR Fulvestrant
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
• Palbociclib + Letrozole OR Fulvestrant
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
• Paclitaxel +/- Tislelizumab
Patients in this arm could receive as the first line of therapy

Locations

Country	Name	City	State
Portugal	Hospital Senhora da Oliveira - Guimarães	Creixomil
Portugal	IPO Lisboa	Lisboa
Portugal	Hospital Beatriz Ângelo	Loures
Portugal	Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE	Porto
Portugal	Centro Hospitalar Vila Nova de Gaia	Vila Nova de Gaia
Spain	Hospital Clínico Universitario de A Coruña	A Coruña	La Coruña
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Institut Català d' Oncologia (ICO Badalona)	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	IOB-Institute of Oncology. Hospital Quironsalud Barcelona	Barcelona
Spain	Vall d´Hebron University Hospital	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Complejo Hospitalario San Pedro de Alcántara	Cáceres
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Institut Català d' Oncologia de Girona (ICO Girona)	Girona
Spain	H. Clínico San Cecilio de Granada	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Institut Català d'Oncologia (ICO Hospitalet)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas
Spain	Complejo Asistencial Universitario de León	León
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Centro Integral Oncológico Clara Campal (CIOCC)	Madrid
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Universitario Morales Meseguer	Murcia
Spain	Hospital Son Llàtzer	Palma de Mallorca	Illes Balears
Spain	Hospital Sant Joan de Reus	Reus
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital General de Catalunya	Sant Cugat Del Vallès	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Clínico Universitario de Santiago CHUS	Santiago De Compostela	La Coruña
Spain	Hospital Quiron Salud Sagrado Corazon Sevilla	Sevilla
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Virgen de la Macarena	Sevilla
Spain	Hospital Universitario de Canarias	Tenerife	Islas Canarias
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncología (IVO)	Valencia
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
United States	Sinai of Baltimore	Baltimore	Maryland
United States	NHOH	Londonderry	New Hampshire
United States	Unv. Wisconsin	Madison	Wisconsin
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Baptist Memorial Health Care	Oxford	Mississippi
United States	Legacy Good Samaritan Hospital and Medical Cente	Portland	Oregon
United States	Carle Cancer Center	Urbana	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
SOLTI Breast Cancer Research Group	Alliance Foundation Trials, LLC., Novartis

Countries where clinical trial is conducted

United States,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	using RECIST 1.1 criteria, as assessed by local radiologists/investigators	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	Progression-free survival 2	defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first	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
Secondary	Overall Survival	the proportion of exitus patients	until patient death, assessed up to approximately 62 months after the first patient enrolled
Secondary	Overall response and clinical benefit	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.	until disease progression or 24 weeks from treatment start.
Secondary	Time to response and duration of response	defined per RECIST 1.1	time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled
Secondary	Adverse events (safety)	Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions	from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled

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