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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06044623
Recruitment Status : Recruiting
First Posted : September 21, 2023
Last Update Posted : April 11, 2024
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

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

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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 related topics: Breast Cancer

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




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  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.

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
Region Örebro County
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
Investigators
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Study Chair: Antonios Valachis, Assoc Prof Region Örebro Län
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Responsible Party: Region Örebro County
ClinicalTrials.gov Identifier: NCT06044623    
Other Study ID Numbers: 280232
First Posted: September 21, 2023    Key Record Dates
Last Update Posted: April 11, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases