To Identify Primary Resistance to CDK4/6 Inhibitors in Breast Cancer

NCT04660435 | Recruiting

• 1 other identifier: Tiresias
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center biomarkers study aiming to prospectively collect biological samples from patients with ER+ and HER2-negative metastatic breast cancer, who are candidate to first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor as per standard clinical practice. Blood and tissue samples will be collected for biomarker analysis, including thymidine kinase1 activity, gene expression signatures and circulating tumor DNA.

Conditions

Metastatic Breast Cancer; ER Positive Breast Cancer; HER2-negative Breast Cancer

Keywords

CDK 4/6 inhibitors; Thymidine Kinase; Palbociclib; Abemaciclib; Ribociclib; circulating tumour DNA; gene expression signatures; aromatase inhibitors

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  time from inclusion date to date of first documentation of progression or death due to any cause, whichever occurs first

  5 years

Secondary Outcomes (1)

• Clinical benefit rate

  5 years

Study Arms (1)

Women with ER+/Her2 negative metastatic breast cancer

Patients with ER+/HER2-negative metastatic breast cancer candidate to first-line treatment with a CDK4/6 inhibitor and an aromatase inhibitor as per standard clinical practice

Diagnostic Test: Thymidine kinase activity

Interventions

Thymidine kinase activity DIAGNOSTIC_TEST

DiviTum® assay determines the enzymatic activity of TK in serum samples

Also known as: Divitum

Women with ER+/Her2 negative metastatic breast cancer

Eligibility Criteria

• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Pre- and post-menopausal patients with luminal (ER-positive and HER2-negative) MBC who have not received prior systemic therapy for MBC, who are candidate to first-line treatment with an aromatase inhibitor and a CDK4/6i as per standard clinical practice. Patients must have evaluable disease according to RECIST 1.1 (either measurable or non-measurable). Patients with bone-only disease will be allowed in a specific sub-cohort, which will comprise 10% of the total sample size.

You may qualify if:

• Women aged 18 years or older, with a diagnosis of metastatic breast cancer
• ER-positive and HER2-negative disease as assessed locally either on primary tumor tissue or on a biopsy of a metastasis
• The patient has not received any prior systemic therapy for metastatic breast cancer (may have received prior hormonal therapy or chemotherapy in the neo/adjuvant setting)
• The patient is candidate to receive first-line therapy with an aromatase inhibitor (AI) and a CDK4/6 inhibitor per local clinical practice
• The patient must have evaluable disease according to RECIST 1.1 (either measurable or non-measurable).
• Note: Patients with bone-only disease will be allowed in a specific sub-cohort, which will comprise 10% of the total sample size.
• Hystologic material from one formalin-fixed, paraffin-embedded (FFPE) tumor block from a diagnostic core or excisional biopsy of a metastatic lesion, taken before study entry must be provided (patients with bone-only disease will be accepted into the trial without a biopsy of the metastatic site). Hystologic material from an additional biopsy (core or excisional) taken at time of disease progression on the study treatment must also be provided, if clinically feasible. When available, hystologic material from an FFPE tumor block from the primary breast cancer must also be submitted.
• The patient agrees to provide blood samples. at the trial specified time points

You may not qualify if:

• Patients with metastatic disease isolated to the central nervous system (CNS) without metastatic involvement of any other site, unless surgical excision of CNS metastasis has been performed and the tumor tissue is available for the study.
• Previous or current non-breast malignancies within the last 5 years, with the exception of in situ carcinoma of the cervix and/or adequately treated basal cell or squamous cell carcinoma of the skin

Sponsors & Collaborators

• Fondazione Sandro Pitigliani: lead
• Clinical Research Technology S.r.l.: collaborator

Study Sites (1)

Hospital Santo Stefano

Prato, Tuscany, 59100, Italy

RECRUITING

Related Publications (1)

• Malorni L, Tyekucheva S, Hilbers FS, Ignatiadis M, Neven P, Colleoni M, Henry S, Ballestrero A, Bonetti A, Jerusalem G, Papadimitriou K, Bernardo A, Seles E, Duhoux FP, MacPherson IR, Thomson A, Davies DM, Bergqvist M, Migliaccio I, Gebhart G, Zoppoli G, Bliss JM, Benelli M, McCartney A, Kammler R, De Swert H, Ruepp B, Fumagalli D, Maibach R, Cameron D, Loi S, Piccart M, Regan MM; International Breast Cancer Study Group; Breast International Group and PYTHIA Collaborators. Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant. Eur J Cancer. 2022 Mar;164:39-51. doi: 10.1016/j.ejca.2021.12.030. Epub 2022 Feb 13.

  PMID: 35172272 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Mandatory: formalin fixed and paraffin embedded (FFPE) tumor block from a baseline biopsy of a metastatic site taken before starting treatment Optional: material from an archival FFPE tumor block from the primary breast tumor Optional: material from one FFPE tumor block of a tissue biopsy from a metastatic site collected upon disease progression to first-line treatment with CDK4/6 inhibitor and AI 24 mL of blood will be collected in EDTA tubes at each time-point Additional 6 ml of whole blood will be collected in EDTA tubes only at baseline

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Luca Malorni

  Azienda USL Toscana Centro - Prato

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luca Malorni

CONTACT

+390574802523; luca.malorni@uslcentro.toscana.it

Chiara Biagioni

CONTACT

+390574802526; chiara.biagioni@uslcentro.toscana.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 9, 2020
• Study Start: September 1, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

IT (1)