Clinical trial NCT06195709: ECLECTIC: EstroTEP and Circulating Biomarkers for ER-positive HER2-negative Metastatic Breast Cancer Patients
Official title: ECLECTIC: EstroTEP and Circulating Biomarkers to Determine the Optimal Second Line Therapy for ER-positive HER2-negative Metastatic Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Carcinoma
Keywords: Metastatic
PET/CT 18F-FES
Circulating markers
Lead sponsor: Institut Curie
Sponsor class: OTHER
Collaborators: name: Zionexa
First posted: 2024-01-08
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized, multicentric, open-label, phase III trial conducted in patients with ER+ HER2- metastatic breast cancer progressing on first line treatment with CDK4/6 inhibitor and aromatase inhibitor, and which aims at evaluating the combined value of 18F-FES PET/CT and circulating biomarkers to guide second line treatment decision between investigator's choice second line endocrine therapy (with or without targeted therapy) and chemotherapy.
Primary purpose: TREATMENT

Brief summary: Eclectic is a strategy trial; once the class of treatment (endocrine therapy or chemotherapy) has been allocated according to 16α-18F-fluoro-17β-oestradiol (18F-FES) Positron Emission Tomography/Computed Tomography (PET/CT) results and circulating tumor biomarkers, clinicians will decide which treatment to use.

Detailed description: All patients deemed eligible for a second line endocrine therapy will undergo a 18F-FES PET/CT scan and circulating tumor biomarkers assessment (circulating tumor cells (CTC) and, if not available, circulating tumor DNA (ctDNA)). All 18F-FES PET/CT scan will be anonymized and reviewed centrally, and compared to the 18Fluorodeoxyglucose (18F-FDG) PET/CT results before treatment initiation; circulating biomarkers status will be assessed centrally and will remain blinded to investigator and patients.

Endocrine therapy in Arm A and C may consist in single agent endocrine therapy or in combination with targeted therapy. Luteinizing Hormone-Releasing Hormone (LH-RH) agonist will be used in combination with endocrine therapy whenever appropriate and per label. Chemotherapy in Arm B may consist in single agent chemotherapy, poly-chemotherapy, or antibody-drug conjugates. Patients who are eligible (per drug label) may receive Poly-adenosine-5'-diphosphate-ribose Polymerase (PARP) inhibitor if allocated to Arm B.

Eligibility criteria: Inclusion Criteria:

1. Metastatic invasive breast carcinoma of no special type.
2. Females of age ≥18 years.
3. Life expectancy \> 3 months.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
5. Estrogen Receptor (ER)-positive (≥10%) and HER2-negative (ASCO/College of American Pathologists guidelines) breast cancer, per local assessment on the most recent breast cancer tissue examined.
6. Tumor block Formalin-Fixed Paraffin-Embedded (primary tumor or metastasis) available.
7. Patients whose disease has progressed on first line endocrine therapy with aromatase inhibitor and CDK4/6 inhibitor and who are deemed eligible, per investigator assessment, to a second line endocrine therapy. The progression on first line endocrine therapy with aromatase inhibitor and CDK4/6 inhibitor must have occurred after more than 6 months on treatment.
8. Patients with available 18F-FDG PET/CT imaging
9. Evaluable disease per RECIST criteria and measurable disease per PERCIST criteria.
10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and any protocol-related procedures including screening evaluations.
11. Signed informed consent.
12. Patient affiliated to a social security system.

Exclusion criteria:

1. Other breast cancer subtype (e.g. invasive lobular breast carcinoma).
2. One or more prior line of chemotherapy in the metastatic setting.
3. Any other antineoplastic therapy given at metastatic disease than the first line therapy with aromatase inhibitor and CDK4/6 inhibitor.
4. Visceral crisis, per investigator's assessment.
5. Liver-only metastases.
6. Prior exposure to any authorized or experimental agent degrading the estrogen receptor (fulvestrant, oral SERDs, PROTAC, etc).
7. Pregnancy or lactation period.
8. In women of childbearing potential or premenopausal women or women with amenorrhea of less than 12 months, without adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization; LH-RH agonist cannot be considered as an efficient contraceptive measure), positive urinary or serum pregnancy test 72 hours before 18F-FES PET/CT.
9. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Patients with a history of CNS metastases or cord compression are eligible if they have been treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable and off anticonvulsants and steroids for at least 4 weeks before treatment start.
10. History of previous cancer or hematological malignancy within 3 years preceding patient enrollment in the trial. Multiple primary breast cancers (controlateral/ipsilateral cancers/local relapses) are allowed pending all tumors were ER+ HER2-.
11. Persons deprived of their freedom or under guardianship or incapable of giving consent.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 54 months
Secondary outcomes:
measure: Progression-Free survival (PFS)
timeFrame: 54 months
measure: Overall survival (OS)
timeFrame: 54 months
measure: Objective response rate (ORR)
timeFrame: 54 months
measure: Clinical benefit rate (CBR)
timeFrame: 24 weeks
measure: Efficacy criteria: PFS at 24 weeks
timeFrame: 24 weeks
measure: Efficacy criteria: OS at 24 weeks
timeFrame: 24 weeks
measure: Efficacy criteria: ORR at 24 weeks
timeFrame: 24 weeks
measure: Efficacy criteria: CBR at 24 weeks
timeFrame: 24 weeks
measure: Safety and toxicity and their relationship to study treatment
timeFrame: 54 months
measure: EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) after 2 months of treatment
timeFrame: 2 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre Francois Baclesse
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: Institut du Cancer Montpellier
city: Nice
country: France
facility: Centre Antoine lacassagne
city: Paris
country: France
facility: Institut Curie
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Cloud
country: France
facility: Institut Curie
city: Saint-Herblain
country: France
facility: Bruno MAUCHERAT
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancerologie de Lorraine
Study officials:
affiliation: Institut Curie
name: Steven Le GOUILL, PhD
role: STUDY_DIRECTOR
References: