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

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ClinicalTrials.gov Identifier: NCT06044623

Recruitment Status : Recruiting

First Posted : September 21, 2023

Last Update Posted : April 11, 2024

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Sponsor:

Collaborators:

University of Patras

University of Florence

Azienda USL Toscana Centro

Helsinki University Central Hospital

Institute for Medical Technology Assessment - the Netherlands

Security Labs Consulting Limited

Circular Economy Foundation

Universidad Nacional de Educación a Distancia

Hellenic Cooperative Oncology Group

University Hospital, Akershus

Uppsala County Council, Sweden

Hospital Clinic of Barcelona

Phaze Clinical Research & Pharma Consulting

Bröstcancerförbundet

Eunomia Ltd

University of Applied Sciences and Arts Northwestern Switzerland

CareAcross Ltd

Örebro University, Sweden

Information provided by (Responsible Party):

Region Örebro County

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer Advanced Breast Cancer Quality of Life Toxicity Older Patients	Drug: CDK 4/6 inhibitors Drug: Endocrine therapy	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	495 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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)
Actual Study Start Date :	March 4, 2024
Estimated Primary Completion Date :	April 2028
Estimated Study Completion Date :	April 2031

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort) -1 level dose reduction as initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 100 mg x 1 for 21 days with 7 days off; or Ribociclib 400 mg x 1 for 21 days with 7 days off; or Abemaciclib 100 mg x 2 daily added to endocrine therapy.	Drug: CDK 4/6 inhibitors Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Active Comparator: Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort) Full initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 125 mg x 1 for 21 days with 7 days off; or Ribociclib 600 mg x 1 for 21 days with 7 days off; or Abemaciclib 150 mg x 2 daily) added to physician's choice endocrine therapy.	Drug: CDK 4/6 inhibitors Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Full initial dose of CDK 4/6-inhibitor (fit patient cohort) Full initial dose of either one of the CDK 4/6-inhibitors: Palbociclib 125 mg x 1 for 21 days with 7 days off; or Ribociclib 600 mg x 1 for 21 days with 7 days off; or Abemaciclib 150 mg x 2 daily) added to physician's choice endocrine therapy.	Drug: CDK 4/6 inhibitors Either Palbociclib, Ribociclib or Abemaciclib Drug: Endocrine therapy Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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.
Overall survival [ Time Frame: Up to 5 years from treatment initiation ]
The time from randomization to death from any cause.
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.
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.
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.
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).
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.
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.

Eligibility Criteria

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Ages Eligible for Study:	70 Years and older (Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06044623

Contacts

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Contact: Antonios Valachis, Assoc Prof	+46196021792	important@oru.se

Locations

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Finland
Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki	Recruiting
Helsinki, Finland
Contact: Peeter Karihtala, Prof peeter.karihtala@hus.fi
Greece
Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital	Not yet recruiting
Athens, Greece
Contact: Helena Linardou, Dr elinardou@otenet.gr
Second Department of Medical Oncology, Hygeia Hospital	Not yet recruiting
Athens, Greece
Contact: Paris Kosmidis, Dr parkosmi@otenet.gr
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School	Not yet recruiting
Patras, Greece
Contact: Angelos Koutras, Prof angkoutr@otenet.gr
Medical Oncology Unit, S. Andrew Hospital	Not yet recruiting
Patras, Greece
Contact: Athina Christopoulou, Dr athinachristo@hotmail.com
Second Department of Medical Oncology, Euromedica General Clinic	Not yet recruiting
Thessaloníki, Greece
Contact: Elena Fountzila, Assoc Prof elenafou@gmail.com
Italy
Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi	Not yet recruiting
Florence, Italy
Contact: Icro Meattini, Assoc Prof icro.meattini@unifi.it
Contact: Luca Visani, Dr l.visani88@gmail.com
"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato	Not yet recruiting
Prato, Italy
Contact: Laura Biganzoli, Prof laura.biganzoli@uslcentro.toscana.it
Contact: Emanuela Risi, Dr emanuela.risi@uslcentro.toscana.it
Norway
Department of Oncology, Akershus University Hospital (AHUS)	Not yet recruiting
Oslo, Norway
Contact: Jürgen Geisler, Prof jurgen.geisler@medisin.uio.no
Contact: Kamilla Fjermeros, Dr Kamilla.Fjermeros@ahus.no
Spain
Department of Medical Oncology, Hospital Clinic of Barcelona	Not yet recruiting
Barcelona, Spain
Contact: Raquel Gomez, Dr ragomez@recerca.clinic.cat
Contact: Montserrat Munoz, Dr mmunoz@clinic.cat
Sweden
Department of Oncology, Uppsala University Hospital	Not yet recruiting
Uppsala, Sweden, 75185
Contact: Hendrik Lindman, Assoc Prof Henrik.lindman@igp.uu.se
Contact: Aglaia Schiza, Dr Aglaia.schiza@igp.uu.se
Department of Oncology, Örebro University Hospital	Recruiting
Örebro, Sweden
Contact: Antonios Valachis, Assoc Prof antonios.valachis@oru.se

Sponsors and Collaborators