Optimizing CDK 4/6-inhibitor doses for older breast cancer patients

Implementing Geriatric Assessment for Dose Optimization of CDK 4/6-inhibitors in Older Breast Cancer Patients - a Pragmatic Randomized-controlled Trial (IMPORTANT Trial)

This study is testing if personalizing the dose of a breast cancer medication for older patients can help them get better results than just lowering the dose based on standard practices.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 495 (estimated)
• Ages: 70 Years and up
• Sex: All
• Sponsor: Region Örebro County (Academic / other)
• Locations: 12 sites (Helsinki and 11 other locations)
• Trial ID: NCT06044623 on ClinicalTrials.gov

What this trial studies

This study focuses on older patients (70 years and above) with advanced hormone receptor-positive and HER2-negative breast cancer who are not candidates for curative treatment. It employs a multicenter, open-label, randomized-controlled design to assess the effectiveness of a comprehensive geriatric assessment (CGA) in determining the appropriate dosing of CDK 4/6-inhibitors combined with endocrine therapy. The goal is to evaluate whether a personalized dosing strategy based on CGA can improve treatment outcomes compared to standard dose reduction practices. Patients will be randomized to receive either the full dose or a reduced dose of the medication based on their CGA results.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 70 and above with advanced HR-positive, HER2-negative breast cancer who have not received prior systemic treatment for their advanced disease.

Not a fit: Patients with curable breast cancer or those who have previously received systemic treatment for advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and safer treatment regimens for older breast cancer patients, enhancing their quality of life.

How similar studies have performed: Other studies have shown promise in using geriatric assessments to tailor cancer treatments, suggesting that this approach may yield beneficial results.

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.

Where this trial is running

Helsinki and 11 other locations

• Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki — Helsinki, Finland (Recruiting)
• Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital — Athens, Greece (Not_yet_recruiting)
• Second Department of Medical Oncology, Hygeia Hospital — Athens, Greece (Not_yet_recruiting)
• Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School — Pátrai, Greece (Not_yet_recruiting)
• Medical Oncology Unit, S. Andrew Hospital — Pátrai, Greece (Not_yet_recruiting)
• Second Department of Medical Oncology, Euromedica General Clinic — Thessaloniki, Greece (Not_yet_recruiting)
• Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi — Florence, Italy (Not_yet_recruiting)
• "Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato — Prato, Italy (Not_yet_recruiting)
• Department of Oncology, Akershus University Hospital (AHUS) — Oslo, Norway (Not_yet_recruiting)
• Department of Medical Oncology, Hospital Clinic of Barcelona — Barcelona, Spain (Not_yet_recruiting)
• Department of Oncology, Örebro University Hospital — Örebro, Sweden (Recruiting)
• Department of Oncology, Uppsala University Hospital — Uppsala, Sweden (Not_yet_recruiting)

Study contacts

• Study coordinator: Antonios Valachis, Assoc Prof

Conditions Metastatic Breast Cancer; Advanced Breast Cancer; Quality of Life; Toxicity; Older Patients