ECLECTIC: EstroTEP and Circulating Biomarkers for ER-positive HER2-negative Metastatic Breast Cancer Patients

Breast Carcinoma Clinical Trial

— ECLECTIC  

Official title:

ECLECTIC: EstroTEP and Circulating Biomarkers to Determine the Optimal Second Line Therapy for ER-positive HER2-negative Metastatic Breast Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06195709
• Other study ID #: IC 2022-12
• Secondary ID: 2023-506282-66-0
• Status: Recruiting
• Phase: Phase 3
• Start date: May 27, 2024
• Est. completion date: September 27, 2029

Study information

• Verified date: June 2024
• Source: Institut Curie
• Contact: François-Clément BIDARD, PhD
• Phone: +33147111515
• Email: francois-clement.bidard[@]curie.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 27, 2029
• Est. primary completion date: September 27, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille
France	Centre Leon Bérard	Lyon
France	Institut Paoli-Calmettes	Marseille
France	Institut du Cancer Montpellier	Montpellier
France	Institut Curie	Paris
France	Centre Eugène Marquis	Rennes
France	Institut Curie	Saint-Cloud
France	Bruno MAUCHERAT	Saint-Herblain

Sponsors (2)

Lead Sponsor	Collaborator
Institut Curie	Zionexa

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is defined as the time from randomization to progression (per RECIST 1.1) or death, among randomized patients.	54 months
Secondary	Progression-Free survival (PFS)	PFS is defined as the time from randomization to progression (per PERCIST 1.0) or death, among randomized patients with available Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) evaluation.	54 months
Secondary	Overall survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause, among randomized patients (arms B and C)	54 months
Secondary	Objective response rate (ORR)	ORR is defined as the proportion of patients who have achieved complete response (CR) or partial response (PR) based on local investigator assessment, among randomized patients with measurable disease at baseline,	54 months
Secondary	Clinical benefit rate (CBR)	CBR at 24 weeks is defined as the proportion of randomized patients who have achieved either a confirmed complete or partial response, or stable disease for at least 24 weeks after treatment start based on local investigator assessment.	24 weeks
Secondary	Efficacy criteria: PFS at 24 weeks	PFS at 24 weeks will be evaluated in patients allocated to arm A.	24 weeks
Secondary	Efficacy criteria: OS at 24 weeks	OS at 24 weeks will be evaluated in patients allocated to arm A.	24 weeks
Secondary	Efficacy criteria: ORR at 24 weeks	ORR at 24 weeks will be evaluated in patients allocated to arm A.	24 weeks
Secondary	Efficacy criteria: CBR at 24 weeks	CBR at 24 weeks will be evaluated in patients allocated to arm A.	24 weeks
Secondary	Safety and toxicity and their relationship to study treatment	Incidence, nature and severity of adverse events (AEs) graded according to NCI CTCAE v5.0	54 months
Secondary	EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) after 2 months of treatment	Questionnaire to measure physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items range from 0 to 100. A higher score represents better function and a higher quality of life.	2 months