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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04660435
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : December 14, 2020
Sponsor:
Collaborator:
Clinical Research Technology S.r.l.
Information provided by (Responsible Party):
Fondazione Sandro Pitigliani

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.


Condition or disease Intervention/treatment
Metastatic Breast Cancer ER Positive Breast Cancer HER2-negative Breast Cancer Diagnostic Test: Thymidine kinase activity

Detailed Description:

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

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.

Criteria

Inclusion Criteria:

  1. Women aged 18 years or older, with a diagnosis of metastatic breast cancer
  2. ER-positive and HER2-negative disease as assessed locally either on primary tumor tissue or on a biopsy of a metastasis
  3. 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)
  4. The patient is candidate to receive first-line therapy with an aromatase inhibitor (AI) and a CDK4/6 inhibitor per local clinical practice
  5. 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.

  6. 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.
  7. The patient agrees to provide blood samples. at the trial specified time points

Exclusion Criteria:

  1. 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.
  2. 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

Information from the National Library of Medicine

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


Contacts
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Contact: Luca Malorni 057480112523 luca.malorni@uslcentro.toscana.it
Contact: Giulio Maria Fusco 0574801110 giuliomaria.fusco@uslcentro.toscana.it

Locations
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Italy
Hospital Santo Stefano Recruiting
Prato, Tuscany, Italy, 59100
Contact: GIULIO FUSCO    3200411550    ml12gmf@gmail.com   
Sponsors and Collaborators
Fondazione Sandro Pitigliani
Clinical Research Technology S.r.l.
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Responsible Party: Fondazione Sandro Pitigliani
ClinicalTrials.gov Identifier: NCT04660435    
Other Study ID Numbers: Tiresias
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: December 14, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Fondazione Sandro Pitigliani:
CDK 4/6 inhibitors
Thymidine Kinase
Palbociclib
Abemaciclib
Ribociclib
circulating tumour DNA
gene expression signatures
aromatase inhibitors
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases