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Trial record 1 of 2 for:    HARMONIA
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Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype (HARMONIA)

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ClinicalTrials.gov Identifier: NCT05207709
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : June 23, 2023
Sponsor:
Collaborators:
Novartis
Alliance Foundation Trials, LLC.
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group

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.


Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Ribociclib + Letrozole OR Fulvestrant Drug: Palbociclib + Letrozole OR Fulvestrant Drug: Paclitaxel +/- Tislelizumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 28, 2022
Estimated Primary Completion Date : March 1, 2026
Estimated Study Completion Date : March 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 +/- Tislelizumab - Exploratory cohort
Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Drug: Paclitaxel +/- Tislelizumab
Patients in this arm could receive as the first line of therapy




Primary Outcome Measures :
  1. Progression-free survival [ 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 ]
    using RECIST 1.1 criteria, as assessed by local radiologists/investigators


Secondary Outcome Measures :
  1. Progression-free survival 2 [ 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 ]
    defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first

  2. Overall Survival [ Time Frame: until patient death, assessed up to approximately 62 months after the first patient enrolled ]
    the proportion of exitus patients

  3. Overall response and clinical benefit [ Time Frame: 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.

  4. Time to response and duration of response [ 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 ]
    defined per RECIST 1.1

  5. Adverse events (safety) [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05207709


Contacts
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Contact: Juan M Ferrero-Cafiero, PharmD 606819182 juan.ferrero@gruposolti.org

Locations
Show Show 52 study locations
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Novartis
Alliance Foundation Trials, LLC.
Investigators
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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 Hospital Clínic of Barcelona / SOLTI cancer research group
Additional Information:
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Responsible Party: SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT05207709    
Other Study ID Numbers: SOLTI-2101
2021-002027-38 ( EudraCT Number )
LEE011A2303R ( Other Identifier: Novartis )
AFT-58 ( Other Identifier: Alliance Foundation Trials, LLC )
First Posted: January 26, 2022    Key Record Dates
Last Update Posted: June 23, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SOLTI Breast Cancer Research Group:
PAM50
intrinsic subtype
HER2-Enriched
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Letrozole
Fulvestrant
Tislelizumab
Palbociclib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors