Clinical trial NCT06044623: Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients
Official title: Implementing Geriatric Assessment for Dose Optimization of CDK 4/6-inhibitors in Older Breast Cancer Patients - a Pragmatic Randomized-controlled Trial (IMPORTANT Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Advanced Breast Cancer
Quality of Life
Toxicity
Older Patients
Lead sponsor: Region Örebro County
Sponsor class: OTHER
Collaborators: name: University of Patras
name: University of Florence
name: Azienda USL Toscana Centro
name: Helsinki University Central Hospital
name: Institute for Medical Technology Assessment - the Netherlands
name: Security Labs Consulting Limited
name: Circular Economy Foundation
name: Universidad Nacional de Educación a Distancia
name: Hellenic Cooperative Oncology Group
name: University Hospital, Akershus
name: Uppsala County Council, Sweden
name: Hospital Clinic of Barcelona
name: Phaze Clinical Research & Pharma Consulting
name: Bröstcancerförbundet
name: Eunomia Ltd
name: University of Applied Sciences and Arts Northwestern Switzerland
name: CareAcross
name: Örebro University, Sweden
First posted: 2023-09-21
Enrollment: 495
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to treatment failure
timeFrame: Up to 5 years from treatment initiation
Secondary outcomes:
measure: Overall treatment utility (OTU)
timeFrame: Three months after treatment initiation
measure: Overall survival
timeFrame: Up to 5 years from treatment initiation
measure: Progression free survival
timeFrame: Up to 5 years from treatment initiation
measure: Time to chemotherapy initiation
timeFrame: Up to 5 years from treatment initiation
measure: Frequency of adverse events
timeFrame: Up to 5 years from treatment initiation
measure: Assessment of Quality of life
timeFrame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
measure: Time until Quality of life deterioration
timeFrame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
measure: Cost effectiveness
timeFrame: Up to 24 months from treatment initiation
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
city: Athens
country: Greece
facility: Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital
city: Athens
country: Greece
facility: Second Department of Medical Oncology, Hygeia Hospital
city: Patras
country: Greece
facility: Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School
city: Patras
country: Greece
facility: Medical Oncology Unit, S. Andrew Hospital
city: Thessaloníki
country: Greece
facility: Second Department of Medical Oncology, Euromedica General Clinic
city: Florence
country: Italy
facility: Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi
city: Prato
country: Italy
facility: "Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato
city: Oslo
country: Norway
facility: Department of Oncology, Akershus University Hospital (AHUS)
city: Barcelona
country: Spain
facility: Department of Medical Oncology, Hospital Clinic of Barcelona
city: Uppsala
country: Sweden
facility: Department of Oncology, Uppsala University Hospital
city: Örebro
country: Sweden
facility: Department of Oncology, Örebro University Hospital
Study officials:
affiliation: Region Örebro Län
name: Antonios Valachis, Assoc Prof
role: STUDY_CHAIR
References: