To Identify Primary Resistance to CDK4/6 Inhibitors in Breast Cancer (TIRESIAS)
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|ClinicalTrials.gov Identifier: NCT04660435|
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : December 14, 2020
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.
|Condition or disease||Intervention/treatment|
|Metastatic Breast Cancer ER Positive Breast Cancer HER2-negative Breast Cancer||Diagnostic Test: Thymidine kinase activity|
Enrolled patients will receive first-line treatment with a CDK4/6 inhibitor + AI (anastrozole, letrozole or exemestane) in accordance with local practice. No drugs will be provided by the study Sponsor. Following disease progression on first-line therapy, subsequent, second-line therapy will be administered at physician discretion and as per physician choice.
For all participating patients, serum and plasma samples will be collected at the following time-points:
- Baseline (< 2 weeks before treatment)
- During treatment with CDK4/6 inhibitors + AI: at day 15 (+/- 2) of the first cycle, day 1 (+/-2) of cycle 2, day 1 (+/- 2) of the cycle closest to the first trial-mandated tumor evaluation (after 12-18 weeks from study inclusion), day 1 (+/- 2) of cycle 6, and every 6 cycles thereafter
- At disease progression or permanent discontinuation of CDK4/6 inhibitors + AI (within 35 days from last CDK4/6 inhibitor dosing)
- During the immediate subsequent treatment (second line) (any type, as per physician choice): at day 1 (+/- 2) of cycle 1 (if > 7 days from last CDK4/6 inhibitors dosing), at day 1 of cycles 3, 6 and every 6 cycles thereafter
- At disease progression or permanent discontinuation of second line treatment (within 35 days from last dosing)
One sample of whole blood will be collected at baseline.
All blood samples will be taken concomitantly with blood draws for routine clinical practice.
To be eligible for the study, availability of material from one formalin fixed and paraffin embedded (FFPE) tumor block from a baseline biopsy of a metastatic site taken before starting treatment is mandatory. Although not mandatory for inclusion, material from an archival FFPE tumor block from the primary breast tumor must also be provided, whenever available. Additionally, 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 in and AI will be collected whenever possible
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||150 participants|
|Target Follow-Up Duration:||5 Years|
|Official Title:||Identification and Monitoring of Resistance to First-line Treatment With CDK 4/6 Inhibitors in Combination With Aromatase Inhibitors in Patients With Metastatic Luminal Breast Cancer Through Non-invasive Biomarkers|
|Actual Study Start Date :||September 1, 2020|
|Estimated Primary Completion Date :||September 1, 2023|
|Estimated Study Completion Date :||September 1, 2025|
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
DiviTum® assay determines the enzymatic activity of TK in serum samples
Other Name: Divitum
- Progression free survival [ Time Frame: 5 years ]time from inclusion date to date of first documentation of progression or death due to any cause, whichever occurs first
- Clinical benefit rate [ Time Frame: 5 years ]Complete Response, Partial Response, or Stable Disease ≥24 weeks
Biospecimen Retention: Samples With DNA
TKa: For TKa analysis, 5 ml of blood will be drawn at each time-point
Tumor tissue: To be eligible for the study, availability of material from one formalin fixed and paraffin embedded (FFPE) tumor block from a baseline biopsy of a metastatic site taken before starting treatment, is mandatory. Although not mandatory for inclusion, material from an archival FFPE tumor block from the primary breast tumor must also be provided, whenever available. Additionally, 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 will be collected whenever possible
ctDNA: ctDNA analysis will be performed on plasma samples. 24 mL of blood will be collected in EDTA tubes at each time-point
Whole blood: 6 ml of whole blood will be collected in EDTA tubes only at baseline
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04660435
|Contact: Luca Malorniemail@example.com|
|Contact: Giulio Maria Fuscofirstname.lastname@example.org|
|Hospital Santo Stefano||Recruiting|
|Prato, Tuscany, Italy, 59100|
|Contact: GIULIO FUSCO 3200411550 email@example.com|