Advanced Breast Cancer, Metastatic Breast Cancer, Older Patients, Quality of Life, Toxicity
Conditions
Brief summary
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.
Interventions
DRUGCDK 4/6 inhibitors
Either Palbociclib, Ribociclib or Abemaciclib
DRUGEndocrine therapy
Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Sponsors
University of Patras
University of Florence
Azienda USL Toscana Centro
Helsinki University Central Hospital
Institute for Medical Technology Assessment - the Netherlands
Security Labs Consulting Limited
Circular Economy Foundation
Universidad Nacional de Educación a Distancia
Hellenic Cooperative Oncology Group
University Hospital, Akershus
Uppsala County Council, Sweden
Hospital Clinic of Barcelona
Phaze Clinical Research & Pharma Consulting
Bröstcancerförbundet
Eunomia Ltd
University of Applied Sciences and Arts Northwestern Switzerland
CareAcross
Örebro University, Sweden
Region Örebro County
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The following inclusion criteria will be applied: 1. Patients male or female aged at least 70 years old at the time of informed consent. 2. 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. 3. Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment. 4. 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. 5. Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end \>12 months. 6. Either measurable disease or non-measurable bone only disease, but evaluable according to RECIST criteria 1.1. 7. Written informed consent prior to any study-specific procedures. 8. Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used. 9. Able to swallow capsules. 10. Able to understand and consent in English language or in native language for each participating country.
Exclusion criteria
Eligible patients will be excluded if they have one of the following criteria: 1. Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors. 2. Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used. 3. Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis. 4. 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. 5. Participating in other interventional trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to treatment failure | Up to 5 years from treatment initiation | The time from randomization to treatment discontinuation because of any reason including disease progression, treatment toxicity, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 5 years from treatment initiation | The time from randomization to death from any cause. |
| Progression free survival | Up to 5 years from treatment initiation | The time from randomization to first documented evidence of disease progression or death from any cause. |
| Time to chemotherapy initiation | Up to 5 years from treatment initiation | The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors. |
| Overall treatment utility (OTU) | Three months after treatment initiation | 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. |
| Assessment of Quality of life | Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first | Quality of life will be assessed using three validated questionnaires, EORTC Quality of Life Questionnaire (QLQ)-C30, Elderly (ELD)-14, and European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L). |
| Time until Quality of life deterioration | Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first | QoL deterioration, defined as the time from randomization until any clinically meaningful worsening (using minimal important differences as cut-off) of any QoL aspect measured by the questionnaires. |
| Cost effectiveness | Up to 24 months from treatment initiation | Resource use, length of life and quality of life data will be collected during the trial for the purpose of conducting an economic evaluation. |
| Frequency of adverse events | Up to 5 years from treatment initiation | Adverse events will be assessed based on adverse events, as graded by CTCAE v 5.0 before each cycle and up to 28 days after the end of CDK 4/6-inhibitors. |
Countries
Finland, Greece, Italy, Norway, Spain, Sweden
Contacts
Primary ContactAntonios Valachis, Assoc Prof
Outcome results
None listed