Back to resultsImplementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients (IMPORTANT)
Primary Purpose
Metastatic Breast Cancer, Advanced Breast Cancer, Quality of Life
Status
Not yet recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CDK 4/6 inhibitors
Endocrine therapy
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer
Eligibility 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.
Sites / Locations
- Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
- Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital
- Second Department of Medical Oncology, Hygeia Hospital
- Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School
- Medical Oncology Unit, S. Andrew Hospital
- Second Department of Medical Oncology, Euromedica General Clinic
- Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi
- "Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato
- Department of Oncology, Akershus University Hospital (AHUS)
- Department of Medical Oncology, Hospital Clinic of Barcelona
- Department of Oncology, Uppsala University Hospital
- Department of Oncology, Örebro University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Other
Arm Label
Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
Full initial dose of CDK 4/6-inhibitor (fit patient cohort)
Arm Description
-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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Overall survival
The time from randomization to death from any cause.
Progression free survival
The time from randomization to first documented evidence of disease progression or death from any cause.
Time to chemotherapy initiation
The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors.
Frequency of adverse events
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
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
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
Resource use, length of life and quality of life data will be collected during the trial for the purpose of conducting an economic evaluation.
Full Information
NCT ID
NCT06044623
First Posted
September 13, 2023
Last Updated
September 19, 2023
Sponsor
Region Örebro County
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
1. Study Identification
Unique Protocol Identification Number
NCT06044623
Brief Title
Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients
Acronym
IMPORTANT
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
April 2028 (Anticipated)
Study Completion Date
April 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Region Örebro County
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
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Advanced Breast Cancer, Quality of Life, Toxicity, Older Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
495 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
Arm Type
Experimental
Arm Description
-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.
Arm Title
Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Full initial dose of CDK 4/6-inhibitor (fit patient cohort)
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CDK 4/6 inhibitors
Intervention Description
Either Palbociclib, Ribociclib or Abemaciclib
Intervention Type
Drug
Intervention Name(s)
Endocrine therapy
Intervention Description
Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Primary Outcome Measure Information:
Title
Time to treatment failure
Description
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 Outcome Measure Information:
Title
Overall treatment utility (OTU)
Description
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
Title
Overall survival
Description
The time from randomization to death from any cause.
Time Frame
Up to 5 years from treatment initiation
Title
Progression free survival
Description
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
Title
Time to chemotherapy initiation
Description
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
Title
Frequency of adverse events
Description
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.
Time Frame
Up to 5 years from treatment initiation
Title
Assessment of Quality of life
Description
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 Frame
Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Title
Time until Quality of life deterioration
Description
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.
Time Frame
Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Title
Cost effectiveness
Description
Resource use, length of life and quality of life data will be collected during the trial for the purpose of conducting an economic evaluation.
Time Frame
Up to 24 months from treatment initiation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonios Valachis, Assoc Prof
Phone
+46196021792
Email
important@oru.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonios Valachis, Assoc Prof
Organizational Affiliation
Region Örebro Län
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
City
Helsinki
Country
Finland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peeter Karihtala, Prof
Email
peeter.karihtala@hus.fi
Facility Name
Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital
City
Athens
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Linardou, Dr
Email
elinardou@otenet.gr
Facility Name
Second Department of Medical Oncology, Hygeia Hospital
City
Athens
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paris Kosmidis, Dr
Email
parkosmi@otenet.gr
Facility Name
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School
City
Patras
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angelos Koutras, Prof
Email
angkoutr@otenet.gr
Facility Name
Medical Oncology Unit, S. Andrew Hospital
City
Patras
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Athina Christopoulou, Dr
Email
athinachristo@hotmail.com
Facility Name
Second Department of Medical Oncology, Euromedica General Clinic
City
Thessaloníki
Country
Greece
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Fountzila, Assoc Prof
Email
elenafou@gmail.com
Facility Name
Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi
City
Florence
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Icro Meattini, Assoc Prof
Email
icro.meattini@unifi.it
First Name & Middle Initial & Last Name & Degree
Luca Visani, Dr
Email
l.visani88@gmail.com
Facility Name
"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato
City
Prato
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Biganzoli, Prof
Email
laura.biganzoli@uslcentro.toscana.it
First Name & Middle Initial & Last Name & Degree
Emanuela Risi, Dr
Email
emanuela.risi@uslcentro.toscana.it
Facility Name
Department of Oncology, Akershus University Hospital (AHUS)
City
Oslo
Country
Norway
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Geisler, Prof
Email
jurgen.geisler@medisin.uio.no
Facility Name
Department of Medical Oncology, Hospital Clinic of Barcelona
City
Barcelona
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raquel Gomez, Dr
Email
ragomez@recerca.clinic.cat
First Name & Middle Initial & Last Name & Degree
Montserrat Munoz, Dr
Email
mmunoz@clinic.cat
Facility Name
Department of Oncology, Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hendrik Lindman, Assoc Prof
Email
Henrik.lindman@igp.uu.se
First Name & Middle Initial & Last Name & Degree
Aglaia Schiza, Dr
Email
Aglaia.schiza@igp.uu.se
Facility Name
Department of Oncology, Örebro University Hospital
City
Örebro
Country
Sweden
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonios Valachis, Assoc Prof
Email
antonios.valachis@oru.se
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients
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