Overcoming Therapy Resistance in ER+ Breast Cancer Patients: a Translational Project (OVERTuRE)

Phase

N/A

Condition

Breast Cancer

Cancer

Treatment

N/A

Clinical Study ID

NCT06129786

CRO-2023-10

Ages > 18
Female

Study Summary

Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after >12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor in association with a CDK4/6i. Disease recurrence in <12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial.

A significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics.

Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Histologically proven diagnosis of adenocarcinoma of the breast with evidence ofmetastatic disease.
ER positive tumor ≥ 1%
HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio < 2.0)
Females, 18 years of age or older
Candidate to first-line endocrine therapy (LH-RH analogue for pre-menopausal women isallowed)
Signed and dated informed consent document indicating that the subject (or legallyacceptable representative) has been informed of all the pertinent aspects of the trialprior to enrollment.
Willingness and ability to comply with scheduled visits, treatment plan, laboratorytests, and other trial procedures.

Exclusion

Exclusion Criteria:

Diagnosis of any secondary malignancy within the last 3 years, except for adequatelytreated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
Prior endocrine therapy for metastatic disease
Prior chemotherapy for metastatic disease
Patients unwilling to or unable to comply with the protocol.
Known CNS metastases

Study Design

May 18, 2023

May 18, 2026

Study Description

Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after >12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor (+/- LH-RH analogue depending from the menopausal status) in association with a CDK4/6i. Disease recurrence in <12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial.

The choice of the endocrine backbone and of the CDK4/6i is mostly influenced by the patient's clinical characteristics and by disease factors.

However, a significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics.

Connect with a study center

Centro di Riferimento Oncologico (CRO) di aviano-IRCCS
Aviano, Pordenone 33081
Italy
Active - Recruiting
Azienda Sanitaria Universitaria del Friuli Centrale(ASUFC)
Udine, 33100
Italy
Active - Recruiting

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