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

April 9, 2024 updated by: Region Örebro County

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

495

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Antonios Valachis, Assoc Prof
  • Phone Number: +46196021792
  • Email: important@oru.se

Study Locations

  • Finland
      • Helsinki, Finland
        • Recruiting
        • Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
        • Contact:
  • Greece
      • Athens, Greece
        • Not yet recruiting
        • Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital
        • Contact:
      • Athens, Greece
        • Not yet recruiting
        • Second Department of Medical Oncology, Hygeia Hospital
        • Contact:
      • Patras, Greece
        • Not yet recruiting
        • Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School
        • Contact:
      • Patras, Greece
        • Not yet recruiting
        • Medical Oncology Unit, S. Andrew Hospital
        • Contact:
      • Thessaloníki, Greece
        • Not yet recruiting
        • Second Department of Medical Oncology, Euromedica General Clinic
        • Contact:
  • Italy
  • Norway
  • Spain
  • Sweden
      • Uppsala, Sweden, 75185
      • Örebro, Sweden
        • Recruiting
        • Department of Oncology, Örebro University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5 years from treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Three months after treatment initiation
Overall survival
Time Frame: Up to 5 years from treatment initiation
The time from randomization to death from any cause.
Up to 5 years from treatment initiation
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.
Up to 5 years from treatment initiation
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.
Up to 5 years from treatment initiation
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.
Up to 5 years from treatment initiation
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).
Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
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.
Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
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.
Up to 24 months from treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Örebro County

Collaborators

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

Investigators

  • Study Chair: Antonios Valachis, Assoc Prof, Region Örebro län

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2024

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2031

Study Registration Dates

First Submitted

September 13, 2023

First Submitted That Met QC Criteria

September 19, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 280232

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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