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

NCT06044623 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 280232
• Study Type: interventional
• Target: 495
• Locations: 6 countries
• Sites: 12

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.

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer; Quality of Life; Toxicity; Older Patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Overall treatment utility (OTU)

  Three months after treatment initiation

• Overall survival

  Up to 5 years from treatment initiation

• Progression free survival

  Up to 5 years from treatment initiation

• Time to chemotherapy initiation

  Up to 5 years from treatment initiation

• Frequency of adverse events

  Up to 5 years from treatment initiation

Study Arms (3)

Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)

EXPERIMENTAL

-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; Drug: Endocrine therapy

Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)

ACTIVE COMPARATOR

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; Drug: Endocrine therapy

Full initial dose of CDK 4/6-inhibitor (fit patient cohort)

OTHER

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; Drug: Endocrine therapy

Interventions

CDK 4/6 inhibitors DRUG

Either Palbociclib, Ribociclib or Abemaciclib

Full initial dose of CDK 4/6-inhibitor (fit patient cohort); Full initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort); Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)

Endocrine therapy DRUG

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 CDK 4/6-inhibitor (vulnerable/frail patient cohort); Lower initial dose of CDK 4/6-inhibitor (vulnerable/frail patient cohort)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (12)

Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki

Helsinki, Finland

RECRUITING

Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital

Athens, Greece

NOT YET RECRUITING

Second Department of Medical Oncology, Hygeia Hospital

Athens, Greece

NOT YET RECRUITING

Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School

Pátrai, Greece

NOT YET RECRUITING

Medical Oncology Unit, S. Andrew Hospital

Pátrai, Greece

NOT YET RECRUITING

Second Department of Medical Oncology, Euromedica General Clinic

Thessaloniki, Greece

NOT YET RECRUITING

Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi

Florence, Italy

NOT YET RECRUITING

"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato

Prato, Italy

NOT YET RECRUITING

Department of Oncology, Akershus University Hospital (AHUS)

Oslo, Norway

NOT YET RECRUITING

Department of Medical Oncology, Hospital Clinic of Barcelona

Barcelona, Spain

NOT YET RECRUITING

Department of Oncology, Örebro University Hospital

Örebro, Sweden

RECRUITING

Department of Oncology, Uppsala University Hospital

Uppsala, 75185, Sweden

NOT YET RECRUITING

Related Publications (1)

• Valachis A, Biganzoli L, Christopoulou A, Fjermeros K, Fountzila E, Geisler J, Gomez-Bravo R, Karihtala P, Kosmidis P, Koutras A, Linardou H, Lindman H, Martinez-Ballestero I, Rodriguez AB, Meattini I, Munoz-Mateu M, Othman M, Psyrri A, Risi E, Schiza A, Spathas N, Utriainen M, Visani L, Ballesteros S, Basdekis I, Hay SD, Fotis T, Fricker S, de Graaf G, Jenset M, Kanters T, Lampropoulos K, Markou C, Mastoraki K, Nanou C, Reales Aviles JM, Santaholma M, Kosmidis T. Implementing geriatric assessment for dose optimization of CDK4/6 inhibitors in older breast cancer patients. Future Oncol. 2024;20(37):2937-2948. doi: 10.1080/14796694.2024.2413841. Epub 2024 Oct 21.

  PMID: 39431459 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Antonios Valachis, Assoc Prof

  Region Örebro län

  STUDY CHAIR

Central Study Contacts

Antonios Valachis, Assoc Prof

CONTACT

+46196021792; important@oru.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 21, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

SE (2); FI (1); IT (2); NO (1); ES (1); GR (5)