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NCT Number: NCT06044623

Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients

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.

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Key information

Conditions

Metastatic Breast Cancer Advanced Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Older Patients Quality of Life Skin Diseases Skin and Connective Tissue Diseases Toxicity

Age range

70 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

The following inclusion criteria will be applied:

  • 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.
  • Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months.
  • Either measurable disease or non-measurable bone only disease, but evaluable according to RECIST criteria 1.1.
  • Written informed consent prior to any study-specific procedures.
  • Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used.
  • Able to swallow capsules.
  • 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:

  • 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.
  • Participating in other interventional trial.

Treatment and study plan

CDK 4/6 inhibitors

Drug

Either Palbociclib, Ribociclib or Abemaciclib

endocrine therapy

Drug

Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor

Primary outcomes

  1. Time to treatment failure

    Time frame: 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 outcomes

  1. Overall treatment utility (OTU)

    Time frame: 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.

  2. Overall survival

    Time frame: Up to 5 years from treatment initiation

    The time from randomization to death from any cause.

  3. Progression free survival

    Time frame: Up to 5 years from treatment initiation

    The time from randomization to first documented evidence of disease progression or death from any cause.

  4. Time to chemotherapy initiation

    Time frame: 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.

  5. Frequency of adverse events

    Time frame: 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.

  6. Assessment of Quality of life

    Time frame: 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).

  7. Time until Quality of life deterioration

    Time frame: 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.

  8. Cost effectiveness

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Antonios Valachis, Assoc Prof

CONTACT

[email protected]

+46196021792

Sponsors and collaborators

Lead sponsor

Region Örebro County

Other

Collaborators

  • Azienda USL Toscana Centro
  • Bröstcancerförbundet
  • CareAcross
  • Circular Economy Foundation
  • Eunomia Ltd
  • Hellenic Cooperative Oncology Group
  • Helsinki University Central Hospital
  • Hospital Clinic of Barcelona
  • Institute for Medical Technology Assessment - the Netherlands
  • Phaze Clinical Research & Pharma Consulting
  • Security Labs Consulting Limited
  • Universidad Nacional de Educación a Distancia
  • University Hospital, Akershus
  • University of Applied Sciences and Arts Northwestern Switzerland
  • University of Florence
  • University of Patras
  • Uppsala County Council, Sweden
  • Örebro University, Sweden

Registry information

Official study title

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

Acronym: IMPORTANT

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Sep 21, 2023
Registry last updated
Nov 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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