EstroTEP and circulating biomarkers for ER-positive HER2-negative metastatic breast cancer patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Curie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 May 2024 → ongoing

Decision date (initial)

2023-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Institut Curie · Zionexa SAS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of chemotherapy (Arm B) versus endocrine therapy (Arm C) as post-CDK4/6 inhibitor second line therapy in ER+ HER2- metastatic breast cancer patients displaying either unfavorable 18F-FES PET/CT features and/or high circulating markers

Secondary objectives 4

1. To further assess the efficacy of chemotherapy (Arm B) versus endocrine therapy (Arm C) in patients displaying either unfavorable 18F-FES PET/CT features and/or high circulating markers
2. To assess the efficacy of endocrine therapy as post-CDK4/6 inhibitor second line therapy, in Arm A (patients with favorable 18F-FES PET/CT features and low CTC count)
3. To evaluate the safety and tolerability of study treatment (chemotherapy or endocrine therapy) and 18F-FES PET/CT
4. To describe the changes in Health-Related Quality of Life (HRQOL)

Conditions and MedDRA coding

Women with ER+ HER2- metastatic breast cancer who progressed on first line therapy with CDK4/6 inhibitor and aromatase inhibitor

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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/CAP guidelines) breast cancer, per local assessment on the most recent breast cancer tissue examined.
6. Tumor block FFPE (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 11

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; LHRH 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 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS), defined as the time from randomization to progression or death, among randomized patients

Secondary endpoints 4

1. Other efficacy endpoints among randomized patients: Progression-free survival (PFS) with available PERCIST tumor evaluation; Overall survival (OS) among randomized patients (arms B and C), Objective response rate (ORR), Clinical benefit rate (CBR) at 24 weeks.
2. Above-mentioned efficacy criteria (PFS, OS, ORR and CBR at 24 weeks) will be evaluated in patients allocated to arm A.
3. Grade 3 or 4 AEs (adverse events) according to NCI CTCAE v5.0, and their relationship to study treatment (chemotherapy or endocrine therapy) will be recorded. For 18F-FES PET/CT, serious adverse events (SAE) and any grade AEs will be collected.
4. QLQ-C30 questionnaire measured at baseline and after 2 months of treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Public contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications