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

Overview

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.

Interventions

• Combination product Endocrine therapy
  Consist in single agent endocrine therapy or in combination with targeted therapy, per guidelines and label. LH-RH agonist will be used in combination with endocrine therapy whenever appropriate and per label.
• Combination product Endocrine therapy combined with the local treatment of FES-negative lesions
  Consist in single agent endocrine therapy or in combination with targeted therapy, per guidelines and label. LH-RH agonist will be used in combination with endocrine therapy whenever appropriate and per label. Cases with only 1 or 2 FES-negative lesions that are accessible to local treatment will be reviewed by the Centralized Reading Committee (including a radiation oncologist) to confirm the feasibility of local treatment.
• Combination product Chemotherapy
  Consist in single agent chemotherapy, poly-chemotherapy, or antibody-drug conjugates, per guidelines and label. Patients who are eligible (per drug label) may receive PARP inhibitor if allocated to Arm B.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: 54 months]

Secondary outcome measures (10)

• Progression-Free survival (PFS) [Time frame: 54 months]
• Overall survival (OS) [Time frame: 54 months]
• Objective response rate (ORR) [Time frame: 54 months]
• Clinical benefit rate (CBR) [Time frame: 24 weeks]
• Efficacy criteria: PFS at 24 weeks [Time frame: 24 weeks]
• Efficacy criteria: OS at 24 weeks [Time frame: 24 weeks]
• Efficacy criteria: ORR at 24 weeks [Time frame: 24 weeks]
• Efficacy criteria: CBR at 24 weeks [Time frame: 24 weeks]
• Safety and toxicity and their relationship to study treatment [Time frame: 54 months]
• EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) after 2 months of treatment [Time frame: 2 months]

Eligibility criteria

Inclusion criteria

• Metastatic invasive breast carcinoma of no special type.
• Females and males of age ≥18 years.
• Life expectancy > 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
• 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.
• Tumor block Formalin-Fixed Paraffin-Embedded (primary tumor or metastasis) available.
• 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.
• Patients with available 18F-FDG PET/CT imaging
• Evaluable disease per RECIST criteria and measurable disease per PERCIST criteria.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and any protocol-related procedures including screening evaluations.
• Signed informed consent.
• Patient affiliated to a social security system.

Exclusion criteria

• Other breast cancer subtype (e.g. invasive lobular breast carcinoma).
• One or more prior line of chemotherapy in the metastatic setting.
• Any other systemic treatment given at metastatic disease than the first line therapy with aromatase inhibitor and CDK4/6 inhibitor.
• Visceral crisis, per investigator's assessment.
• Liver-only metastases.
• Prior exposure to any authorized or experimental agent degrading the estrogen receptor (fulvestrant, oral SERDs, PROTAC, etc).
• Pregnancy or lactation period.
• 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.
• 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.
• 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-.
• Persons deprived of their freedom or under guardianship or incapable of giving consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 21 centers

• Centre Hospitalier de la Côte basque — Bayonne
• Institut Bergonié — Bordeaux
• Polyclinique Bordeaux Nord Aquitaine — Bordeaux
• Centre Francois Baclesse — Caen
• Centre Georges Francois Leclerc — Dijon
• Centre Oscar Lambret — Lille
• CHU Limoges — Limoges
• Centre Leon Bérard — Lyon
• … and 13 more centers

Identifiers

NCT: NCT06195709 · IC 2022-12 · 2023-506282-66-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗