About this trial
IMPORTANT study is a multicenter, open-label, prospective, randomized-controlled, non-inferiority trial with a pragmatic approach involving older patients (≥ 70 years old) with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, not amenable for curative treatment and without prior therapy for advanced disease, who are suitable to receive CDK 4/6-inhibitors plus endocrine therapy as first line therapy. The study implements two approaches with high level of evidence, namely the use of comprehensive geriatric assessment (CGA) approach in treatment decision making and the use of CDK 4/6-inhibitors as the initial treatment of choice, to investigate whether a common clinical practice (starting dose reduction of CDK 4/6-inhibitors in older patients) with evidence of low certainty can be standardized using a more individualized-based approach.
On the basis of baseline CGA assessment, patients will either receive full dose of CDK 4/6-inhibitors plus endocrine therapy (if patients are fit according to CGA) or be randomized to full dose vs. reduced initial dose of CDK 4/6-inhibitors (if vulnerable or frail according to CGA). The study hypothesis is that adjusting the dose according to vulnerability will allow patients to tolerate treatment better without jeopardizing the treatment efficacy.
This project has received funding from the European Union's HORIZON 2022 research and innovation actions supporting the implementation of the Mission on Cancer under grant agreement No 101104589.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients male or female aged at least 70 years old at the time of informed consent.
Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory.
Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment.
No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed.
Disqualifiers
Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors.
Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used.
Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis.
History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
Trial design
Parallel
Treatments tested in this trial
CDK 4/6 inhibitors
DrugEither Palbociclib, Ribociclib or Abemaciclib
Endocrine therapy
DrugEither Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Treatment groups
Trial outcomes
Primary outcomes
Time to treatment failure
The time from randomization to treatment discontinuation because of any reason including disease progression, treatment toxicity, or death due to any cause.
Secondary outcomes
Overall treatment utility (OTU)
A composite endpoint that will be assessed at the first efficacy evaluation. OTU incorporates objective and participant-reported outcome measures of anticancer efficacy, tolerability and acceptability of treatment providing a simple "good, intermediate or poor" categorization of outcome.
Overall survival
The time from randomization to death from any cause.
Progression free survival
The time from randomization to first documented evidence of disease progression or death from any cause.
Time to chemotherapy initiation
The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors.
Sponsors and contacts
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Region Örebro County
Lead sponsor
University of Patras
Collaborator
University of Florence
Collaborator
Azienda USL Toscana Centro
Collaborator
Helsinki University Central Hospital
Collaborator
Institute for Medical Technology Assessment - the Netherlands
Collaborator
Security Labs Consulting Limited
Collaborator
Circular Economy Foundation
Collaborator
Universidad Nacional de Educación a Distancia
Collaborator
Hellenic Cooperative Oncology Group
Collaborator
University Hospital, Akershus
Collaborator
Uppsala County Council, Sweden
Collaborator
Hospital Clinic of Barcelona
Collaborator
Phaze Clinical Research & Pharma Consulting
Collaborator
Bröstcancerförbundet
Collaborator
Eunomia Ltd
Collaborator
University of Applied Sciences and Arts Northwestern Switzerland
Collaborator
CareAcross
Collaborator
Örebro University, Sweden
Collaborator