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

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age70+
SponsorRegion Örebro County

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

Treatment groups

495 Participants
are divided into 3 treatment groups
Group A: Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)Experimental treatment 2 interventions
Group B: Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)Active comparator 2 interventions
Group C: Full initial dose of CDK 4/6-inhibitor (fit patient cohort)Other 2 interventions

Trial outcomes

Primary outcomes

1

Time to treatment failure

The time from randomization to treatment discontinuation because of any reason including disease progression, treatment toxicity, or death due to any cause.

Time frame
Up to 5 years from treatment initiation

Secondary outcomes

1

Overall treatment utility (OTU)

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.

Time frame
Three months after treatment initiation
2

Overall survival

The time from randomization to death from any cause.

Time frame
Up to 5 years from treatment initiation
3

Progression free survival

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

Time frame
Up to 5 years from treatment initiation
4

Time to chemotherapy initiation

The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors.

Time frame
Up to 5 years from treatment initiation

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Region Örebro County

Lead sponsor

University of Patras

Collaborator

University of Florence

Collaborator

Azienda USL Toscana Centro

Collaborator

Helsinki University Central Hospital

Collaborator

Institute for Medical Technology Assessment - the Netherlands

Collaborator

Security Labs Consulting Limited

Collaborator

Circular Economy Foundation

Collaborator

Universidad Nacional de Educación a Distancia

Collaborator

Hellenic Cooperative Oncology Group

Collaborator

University Hospital, Akershus

Collaborator

Uppsala County Council, Sweden

Collaborator

Hospital Clinic of Barcelona

Collaborator

Phaze Clinical Research & Pharma Consulting

Collaborator

Bröstcancerförbundet

Collaborator

Eunomia Ltd

Collaborator

University of Applied Sciences and Arts Northwestern Switzerland

Collaborator

CareAcross

Collaborator

Örebro University, Sweden

Collaborator