Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.
About the trial
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.
Original English text from ClinicalTrials.gov
Who can (and can't) join
✓ Qualifies
- •Wiek co najmniej 18 lat
- •Potwierdzona histologicznie lub cytologicznie diagnoza raka piersi z zaawansowaną chorobą, która nie może być operowana lub leczona promieniami, bądź nowotwór rozsiany nienadający się do kuracyjnego leczenia
- •Odpowiedni kandydat do terapii hormonalnej (bez ostrego pogorszenia stanu, bez szybko postępującej choroby)
- •Mierzalne ogniska nowotworowe lub samotne ogniska kostne z widocznym zajęciem, z co najmniej 1 zmianą lityczną lub mieszaną
- •Co najmniej 50% mierzalnych ognisk wykazuje wysoki pobór radioaktywnych znaczników w badaniu PET
- •Receptory hormonalne dodatnie (HR+) i receptor HER2 ujemny (HER2-) w ostatniej biopsji
- •Progresja choroby podczas lub w ciągu 28 dni po zakończeniu leczenia inhibitorem CDK4/6 w kombinacji z anastrozolem lub letrozolem, zastosowanym po raz pierwszy przy chorobie rozsianych
- •Sprawność fizyczna ECOG 0 lub 1 (pacjent może wykonywać codzienne czynności)
✗ Disqualifies
- •Wcześniejsze leczenie fulwestrantem lub innymi podobnymi lekami (SERD/antagoniści receptora estrogenowego)
- •Wcześniejsze leczenie tamoksyfenem lub SERD w chorobie rozsianych
- •Inne leczenie hormonalne mniej niż 14 dni przed rozpoczęciem badania
- •Wcześniejsze leczenie inhibitorem CDK4/6 po pierwszej linii w chorobie rozsianych
- •Bisfosfoniary lub inhibitory RANKL rozpoczęte lub zmieniona dawka mniej niż 3 miesiące przed badaniem
- •Radioterapia w ciągu 14 dni (28 dni dla zmian w mózgu) przed badaniem
Simplified criteria — AI translation
Trial details
- Minimum age
- 18 Years
- Last updated (source)
- May 14, 2026
- Sex
- No restrictions
Therapies / drugs in trial
Locations (1)
European Institute of Oncology
Milan, Italy
Trial contact
Giuseppe Curigliano, MD
Carmine Valenza, MD
Contact information from ClinicalTrials.gov. Contact in English.
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Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.
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