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Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)

NCT07395336 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2026-05-14

No results posted yet for this study

Summary

Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with CDK4/6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.

Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the HR loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.

Recently, the 16a-\[18F\]fluoro-17b-estradiol positron emission tomography (\[18F\]FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.

Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with target cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.

Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the Hormon Receptor (HR) loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.

Recently, the 16a-\[18F\] fluoro-17b-estradiol positron emission tomography (\[18F\] FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.

The combination of endocrine agent, namely fulvestrant 250 mg plus anastrozole 1 mg (an aromatase inhibitor), demonstrated to provide an overall survival benefit in patients with Hormon Receptor positive Breast Cancer only in first line setting but not in patients progressing to ET. However, meanwhile, fulvestrant 500 mg was demonstrated to be superior to fulvestrant 250 mg in 2nd line setting, and oral SERDs (e.g. Elacestrant, Camizestrant) were demonstrated to be superior in terms of Progression Free Survival to fulvestrant 500 mg in patients progressing on ET, in the subgroup of patients with estrogen receptor 1 gene (ESR1) mutations.

Hypothesis: there is a strong rationale to assess the safety and the activity of Elacestrant plus exemestane in patients with pre-treated HR+ and Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and at least 50% of \[18F\]FES-avid measurable lesions, using \[18F\]FES PET/CT to evaluate the early response to treatment.

Conditions

Interventions

DRUG

elacestrant and exemestane

elacestrant 345 mg die and exemestane 25 mg die

Sponsors & Collaborators

  • European Institute of Oncology

    lead OTHER

Principal Investigators

  • Giuseppe Curigliano · European Institute of Oncology

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-05-11
Primary Completion
2028-12-31
Completion
2028-12-31

Countries

  • Italy

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07395336 on ClinicalTrials.gov