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

280232

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.

2024-03-04

2028-04-01

2031-04-01

Recruiting

Early phase I

495

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 495, 'type': 'ESTIMATED'}}

2024-04-11