Mechanisms of Response and Resistance to Innovative Treatments in Patients With Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT07066917

Last Updated: 2025-07-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-10-15

Study Completion Date

2029-10-31

Brief Summary

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Ample evidence has highlighted the significant clinical benefit of novel therapies for many patients with advanced breast cancer (aBC). The use of CDK inhibitors, antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), and PARP inhibitors as first-line or subsequent treatments has improved progression-free survival (PFS) rates compared to conventional therapies. In selected cases, these treatments have also increased overall survival (OS), reshaping the therapeutic landscape for advanced breast cancer.

However, several key questions remain unanswered. For example, what should be the first-line treatment when multiple effective options are available? Determining the optimal sequence of drugs in successive lines of therapy is another major challenge. Furthermore, the development of resistance to treatment and the occurrence of severe adverse events that may lead to early discontinuation or fatal outcomes are pressing concerns.

That said, identifying robust predictive biomarkers of response or resistance is crucial for ensuring that patients receive the most effective treatment while avoiding unnecessary exposure to therapies that could cause harm without benefit. Additionally, when multiple effective options exist, selecting the optimal treatment algorithm for each patient based on clinical, pathological, and molecular biomarkers is essential.

We herein, aim at employing high throughput methodologies, such as Whole Exome Sequencing, circulating tumour DNA (ctDNA) analysis, digital pathology and radiomics analyses, as well as real-world data obtained both from patients records for the training of a ML-based algorithm that can predict response or resistance to a specific treatment, based on the genetic make-up of the patient and the molecular profile of the tumour.

Detailed Description

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Conditions

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Metastatic Breast Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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ADCs

Patients receiving treatment with an Antibody-Drug conjugate (e.g Trastuzumab-Deruxtecan, Sacituzumab-Govitecan)

No interventions assigned to this group

ICIs

Patients receiving treatment with an immune checkpoint inhibitor (ICI) (e.g pembrolizumab)

No interventions assigned to this group

PARPi

Patients receiving treatment with a PARP inhibitor (e.g Olaparib)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Eligible patients will be 18 years of age and older
* Histologically confirmed, advanced breast cancer.
* Diagnosis of i) hormone receptor positive and/or ii) HER2-positive or -low or iii) triple negative breast cancer (TNBC).
* Patients will be included in the analysis after receiving at least one treatment cycle.

Exclusion Criteria

* Diagnosis of early breast cancer at time of enrollment
* Unwillingness to provide informed consent
* Unwillingness to provide biological specimen
* Lack of comprehensive clinical data
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hellenic Cooperative Oncology Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elena Fountzilas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hellenic Cooperative Oncology Group

Locations

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University General Hospital "ATTIKON", 2nd propedeutic dept. of Internal Medicine

Athens, , Greece

Site Status RECRUITING

"MITERA" Hospital, Dept. of Medical Oncology

Athens, , Greece

Site Status RECRUITING

Metropolitan Hospital, 2nd Dept. of Medical Oncology

Athens, , Greece

Site Status RECRUITING

Metropolitan Hospital, 4th Dept. of Medical Oncology

Athens, , Greece

Site Status RECRUITING

St. Luke's Hospital, Dept. of Medical Oncology

Thessaloniki, , Greece

Site Status RECRUITING

Countries

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Greece

Central Contacts

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Electra Sofou, PhD

Role: CONTACT

+302106912520 ext. 16

Elena Fountzilas, MD, PhD

Role: CONTACT

+302106912520

Facility Contacts

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Georgia Gomatou, MD, PhD

Role: primary

+306973598542

Pinelopi Stamoulou

Role: primary

+30210 686 9223

Eleni Aravantinou, MD, MSc

Role: primary

+306932443612

Asimina Pelteki

Role: primary

+306981731673

Elena Fountzilas, MD, PhD

Role: primary

+306945779709

Iliana Tapazidou-Spanoudi

Role: backup

+306988157958

References

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Reference Type BACKGROUND
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D'Arienzo A, Verrazzo A, Pagliuca M, Napolitano F, Parola S, Viggiani M, Caputo R, Puglisi F, Giuliano M, Del Mastro L, Arpino G, De Laurentiis M, Montemurro F. Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations. EClinicalMedicine. 2023 Jul 27;62:102113. doi: 10.1016/j.eclinm.2023.102113. eCollection 2023 Aug.

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Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. doi: 10.1056/NEJMoa1809615. Epub 2018 Oct 20.

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Reference Type BACKGROUND
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Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.

Reference Type BACKGROUND
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Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Loirat D, Tredan O, Ciruelos E, Dalenc F, Gomez Pardo P, Jhaveri KL, Delaney R, Valdez T, Wang H, Motwani M, Yoon OK, Verret W, Tolaney SM. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Oct 21;402(10411):1423-1433. doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23.

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Reference Type BACKGROUND
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Other Identifiers

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HE_11PDR/24

Identifier Type: -

Identifier Source: org_study_id

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