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

Quality of Life Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06044623
• Other study ID #: 280232
• Status: Recruiting
• Phase: Phase 3
• Start date: March 4, 2024
• Est. completion date: April 2031

Study information

• Verified date: April 2024
• Source: Region Örebro County
• Contact: Antonios Valachis, Assoc Prof
• Phone: +46196021792
• Email: important[@]oru.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 495
• Est. completion date: April 2031
• Est. primary completion date: April 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Metastatic Breast Cancer
• Older Patients
• Quality of Life
• Toxicity

Intervention

Drug:
• CDK 4/6 inhibitors
Either Palbociclib, Ribociclib or Abemaciclib
• Endocrine therapy
Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor

Locations

Country	Name	City	State
Finland	Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki	Helsinki
Greece	Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital	Athens
Greece	Second Department of Medical Oncology, Hygeia Hospital	Athens
Greece	Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School	Patras
Greece	Medical Oncology Unit, S. Andrew Hospital	Patras
Greece	Second Department of Medical Oncology, Euromedica General Clinic	Thessaloníki
Italy	Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi	Florence
Italy	"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato	Prato
Norway	Department of Oncology, Akershus University Hospital (AHUS)	Oslo
Spain	Department of Medical Oncology, Hospital Clinic of Barcelona	Barcelona
Sweden	Department of Oncology, Örebro University Hospital	Örebro
Sweden	Department of Oncology, Uppsala University Hospital	Uppsala

Sponsors (19)

Lead Sponsor

Collaborator

Region Örebro County

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

Countries where clinical trial is conducted

Finland,  Greece,  Italy,  Norway,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 years from treatment initiation
Secondary	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.	Three months after treatment initiation
Secondary	Overall survival	The time from randomization to death from any cause.	Up to 5 years from treatment initiation
Secondary	Progression free survival	The time from randomization to first documented evidence of disease progression or death from any cause.	Up to 5 years from treatment initiation
Secondary	Time to chemotherapy 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
Secondary	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.	Up to 5 years from treatment initiation
Secondary	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).	Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Secondary	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.	Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Secondary	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.	Up to 24 months from treatment initiation