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

April 17, 2024 updated by: Institut Curie

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Arm A: Endocrine therapy
  1. Patients in whom all tumor sites display a FES SUVmax ≥2 AND who have low levels of circulating tumor biomarkers will be treated with endocrine therapy.
  2. Patients in whom 18F-FES PET shows an heterogenous uptake, with one or maximum two tumor sites with low FES uptake (SUVmax <2) that represent less than 20% of all tumor sites and are deemed accessible to local treatment (e.g. stereotactic radiation therapy or another equivalent local therapy) will be treated, if they have low levels of circulating tumor biomarkers, by 2nd line endocrine therapy in Arm A, combined with the local treatment of FES-negative lesions.
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.
Other Names:
  • Standardized endocrine therapy regimen
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.
Other Names:
  • Standardized endocrine therapy regimen
Active Comparator: Arm B: Chemotherapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
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.
Other Names:
  • Standardized endocrine therapy regimen
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.
Other Names:
  • Standardized chemotherapy regimen
Active Comparator: Arm C: Endocrine therapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
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.
Other Names:
  • Standardized endocrine therapy regimen
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.
Other Names:
  • Standardized chemotherapy regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 54 months
PFS is defined as the time from randomization to progression (per RECIST 1.1) or death, among randomized patients.
54 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free survival (PFS)
Time Frame: 54 months
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
Overall survival (OS)
Time Frame: 54 months
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
Objective response rate (ORR)
Time Frame: 54 months
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
Safety and toxicity and their relationship to study treatment
Time Frame: 54 months
Incidence, nature and severity of adverse events (AEs) graded according to NCI CTCAE v5.0
54 months
EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) after 2 months of treatment
Time Frame: 2 months
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
Clinical benefit rate (CBR)
Time Frame: 24 weeks
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
Efficacy criteria: PFS at 24 weeks
Time Frame: 24 weeks
PFS at 24 weeks will be evaluated in patients allocated to arm A.
24 weeks
Efficacy criteria: OS at 24 weeks
Time Frame: 24 weeks
OS at 24 weeks will be evaluated in patients allocated to arm A.
24 weeks
Efficacy criteria: ORR at 24 weeks
Time Frame: 24 weeks
ORR at 24 weeks will be evaluated in patients allocated to arm A.
24 weeks
Efficacy criteria: CBR at 24 weeks
Time Frame: 24 weeks
CBR at 24 weeks will be evaluated in patients allocated to arm A.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Curie

Collaborators

Zionexa

Investigators

  • Study Director: Steven Le GOUILL, PhD, Institut Curie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2024

Primary Completion (Estimated)

August 15, 2028

Study Completion (Estimated)

August 15, 2029

Study Registration Dates

First Submitted

December 7, 2023

First Submitted That Met QC Criteria

December 22, 2023

First Posted (Actual)

January 8, 2024

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IC 2022-12
  • 2023-506282-66-00 (Registry Identifier: EU trial number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

IPD Sharing Access Criteria

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Carcinoma

Clinical Trials on Endocrine therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe