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

Sponsor

SOLTI Breast Cancer Research Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT05207709

Collaborator

Novartis (Industry), Alliance Foundation Trials, LLC. (Other)

456

Enrollment

Locations

Arms

59.1

Anticipated Duration (Months)

10.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 80 sites worldwide.

In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel. 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Ribociclib + Letrozole OR Fulvestrant Drug: Palbociclib + Letrozole OR Fulvestrant Drug: Paclitaxel	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

456 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 28, 2022

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ribociclib + Endocrine Therapy Ribociclib + Fulvestrant or Letrozole	Drug: Ribociclib + Letrozole OR Fulvestrant Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Experimental: Palbociclib + Endocrine Therapy Palbociclib + Fulvestrant or Letrozole	Drug: Palbociclib + Letrozole OR Fulvestrant Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Experimental: Paclitaxel - Exploratory cohort Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.	Drug: Paclitaxel Patients in this arm could receive as the first line of therapy

Arm

Intervention/Treatment

Experimental: Ribociclib + Endocrine Therapy

Ribociclib + Fulvestrant or Letrozole

Drug: Ribociclib + Letrozole OR Fulvestrant

Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks

Experimental: Palbociclib + Endocrine Therapy

Palbociclib + Fulvestrant or Letrozole

Drug: Palbociclib + Letrozole OR Fulvestrant

Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks

Experimental: Paclitaxel - Exploratory cohort

Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.

Drug: Paclitaxel

Patients in this arm could receive as the first line of therapy

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Senhora da Oliveira - Guimarães	Creixomil		Portugal
2	IPO Lisboa	Lisboa		Portugal	1500-650
3	Hospital Beatriz Ângelo	Loures		Portugal	2674-514
4	Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE	Porto		Portugal	4200-072
5	Centro Hospitalar Vila Nova de Gaia	Vila Nova de Gaia		Portugal	4434-502
6	Institut Català d' Oncologia (ICO Badalona)	Badalona	Barcelona	Spain	08916
7	Institut Català d'Oncologia (ICO Hospitalet)	Hospitalet de Llobregat	Barcelona	Spain	08908
8	Hospital General de Catalunya	Sant Cugat Del Vallès	Barcelona	Spain	08195
9	Hospital Son Llàtzer	Palma de Mallorca	Illes Balears	Spain	07198
10	Hospital Universitario de Canarias	Tenerife	Islas Canarias	Spain	38320
11	Hospital Clínico Universitario de A Coruña	A Coruña	La Coruña	Spain	15006
12	Hospital Clínico Universitario de Santiago CHUS	Santiago De Compostela	La Coruña	Spain	15706
13	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid	Spain	28942
14	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
15	Hospital General Universitario de Alicante	Alicante		Spain	03010
16	Hospital del Mar	Barcelona		Spain	08003
17	Vall d´Hebron University Hospital	Barcelona		Spain	08035
18	Hospital Clinic de Barcelona	Barcelona		Spain	08036
19	IOB-Institute of Oncology. Hospital Quironsalud Barcelona	Barcelona		Spain	8023
20	Hospital de Basurto	Bilbao		Spain	48013
21	Complejo Hospitalario San Pedro de Alcántara	Cáceres		Spain	10003
22	Institut Català d' Oncologia de Girona (ICO Girona)	Girona		Spain	17007
23	Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
24	H. Clínico San Cecilio de Granada	Granada		Spain	18016
25	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas		Spain	35010
26	Complejo Asistencial Universitario de León	León		Spain	24001
27	Hospital Universitari Arnau de Vilanova de Lleida	Lleida		Spain	25198
28	Hospital Universitario La Princesa	Madrid		Spain	28006
29	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
30	Fundación Jiménez Díaz	Madrid		Spain	28040
31	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
32	Hospital La Paz	Madrid		Spain	28046
33	Centro Integral Oncológico Clara Campal (CIOCC)	Madrid		Spain	28050
34	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid		Spain	28222
35	Hospital Virgen de la Victoria	Malaga		Spain	29010
36	Hospital Universitario Morales Meseguer	Murcia		Spain	30008
37	Hospital Sant Joan de Reus	Reus		Spain	43204
38	Hospital Universitario de Salamanca	Salamanca		Spain	37007
39	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
40	Hospital Virgen de la Macarena	Sevilla		Spain	41007
41	Hospital Quiron Salud Sagrado Corazon Sevilla	Sevilla		Spain	41013
42	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
43	Instituto Valenciano de Oncología (IVO)	Valencia		Spain	46009
44	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
45	Hospital Clínico Universitario Lozano Blesa	Zaragoza		Spain	50009

Sponsors and Collaborators

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

Investigators

Principal Investigator: Aleix Prat, MD, Hospital Clínic of Barcelona / SOLTI
Principal Investigator: Lisa A Carey, MD, UNC Lineberger Comprehensive Cancer Center
Principal Investigator: Dan G Stover, MD, Stefanie Spielman Comprehensive Breast Center
Principal Investigator: Tomás Pascual, MD, SOLTI Breast Cancer Research Group