Actively Recruiting
Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
Led by European Institute of Oncology · Updated on 2026-05-14
26
Participants Needed
1
Research Sites
133 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official Title
Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Must be at least 18 years old
- Have a confirmed diagnosis of breast cancer that is locally advanced or metastatic and not curable by surgery or radiation
- Suitable candidates for endocrine therapy without visceral crisis or rapidly progressing disease
- Have measurable disease or bone-only disease with at least one evaluable lytic or mixed bone lesion
- Have at least 50% of measurable lesions showing avid uptake on 18F-FES PET/CT
- Have hormone receptor-positive and HER2-negative disease confirmed by recent biopsy
- Must have progressed during or within 28 days after prior treatment with a CDK4/6 inhibitor combined with anastrozole or letrozole (plus LHRH agonist if applicable)
- Prior CDK4/6 inhibitor treatment must have been in first line metastatic setting with at least 12 months of disease control
- No other treatment after the CDK4/6 inhibitor plus endocrine therapy
- ECOG performance status of 0 or 1
You will not qualify if you...
- Prior treatment with fulvestrant, elacestrant, or investigational SERD or ER antagonists in metastatic or early disease
- Prior treatment with tamoxifen or SERD alone or combined with CDK4/6 inhibitors in metastatic setting
- Received any endocrine therapy less than 14 days before starting study drug
- Any prior treatment after first line with CDK4/6 inhibitors in metastatic setting
- Bisphosphonates or RANKL inhibitors started or dose changed within 3 months before study drug
- Radiation therapy within 14 days (28 days for brain lesions) before starting study drug
AI-Screening
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Trial Site Locations
Total: 1 location
1
European Institute of Oncology
Milan, Italy, Italy, 20141
Actively Recruiting
Research Team
G
Giuseppe Curigliano, MD
CONTACT
C
Carmine Valenza, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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