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

NCT06129786 | Recruiting

• 1 other identifier: CRO-2023-10
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 ABC.

  Mean difference in mean VAF in most frequently mutated gene found at baseline, with respect to first evaluation after 15 days between responders (CR-PR-SD, Complete Response - Partial Response - Stable Disease) and non-responders (PD, Progressive Disease)

  up to 3 years

• 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 ABC.

  Mean difference in mean VAF in most frequently mutated gene found at baseline, with respect to 6 months evaluation between responders (CR-PR-SD, Complete Response - Partial Response - Stable Disease) and non-responders (PD, Progressive Disease)

  up to 3 years

Secondary Outcomes (4)

• To explore the impact of ctDNA-based biomarkers in terms of treatment resistance

  from first biomarker assessment until objective PD or end of follow-up, up to 3 years

• To explore the impact of ctDNA-based biomarkers in terms of survival

  from beginning of the therapy until objective PD, death or end of follow-up, up to 3 years

• To explore the impact of ctDNA-based biomarkers in terms of survival

  from beginning of the therapy until death from any cause or end of follow-up, up to 3 years

• Mean difference in mean VAF in most frequently mutated gene found at baseline, between baseline and progression in non-responders (PD, Progressive Disease)

  up to 3 years

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women with hormone receptor-positive ABC, considered eligible for endocrine therapy as first line endocrine treatment

You may qualify if:

• Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic 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 is allowed)
• Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

You may not qualify if:

• Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated 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

Sponsors & Collaborators

• Centro di Riferimento Oncologico - Aviano: lead

Study Sites (2)

Centro di Riferimento Oncologico (CRO) di aviano-IRCCS

Aviano, Pordenone, 33081, Italy

RECRUITING

Azienda Sanitaria Universitaria del Friuli Centrale(ASUFC)

Udine, 33100, Italy

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Fabio Puglisi, MD,PhD

  Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS

  PRINCIPAL INVESTIGATOR

• Barbara Belletti, PhD

  Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabio Puglisi, MD, PhD

CONTACT

+39 0434 659253; fabio.puglisi@cro.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 13, 2023
• Study Start: May 18, 2023
• Primary Completion: May 18, 2026
• Study Completion: May 18, 2026
• Last Updated: November 13, 2023

Record last verified: 2023-11

Locations

IT (2)