An international, multicenter, randomised, superiority phase III, open label, 2-arm study to investigate distant metastasis free survival with elacestrant compared with standard endocrine therapy patients with ctDNA+ ER+/HER2- early breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Feb 2024 → ongoing

Decision date (initial)

2023-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

A.MRBS - A. Menarini Research & Business Service GmbH

External identifiers

EU CT number

2022-501453-36-00

ClinicalTrials.gov

NCT05512364

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others, Efficacy, Safety, Therapy

To evaluate whether elacestrant can delay occurrence of distant metastasis or death when compared to standard endocrine therapy in ER+/HER2- breast cancer patients with ctDNA-relapse.

Secondary objectives 4

1. To evaluate invasive disease-free survival (iDFS), relapse-free survival (RFS) and overall survival (OS) between the 2 treatment arms
2. To characterize the safety and the tolerability of the 2 treatment arms
3. To establish the patient-reported tolerability profile in each treatment arm
4. To compare the patient-reported benefit between the two treatment arms

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. ctDNA screening phase: Female (both pre- and postmenopausal) or male patients with histologically confirmed ER positive (regardless of PR), HER2 negative breast cancer, according to local pathologist: ER-positive defined as ≥ 10% of cells staining positive for ER or Allred proportion score ≥3; HER2-negative defined as a score of 0, 1+ by immunohistochemistry (IHC) or a negative in situ hybridization (ISH) based on single-probe average HER2 copy number, as per American Society of Clinical Oncology guidelines
2. Randomised trial: Absence of locoregional and/or metastatic disease and/or new malignancy, as investigated by: Mammogram (unilateral in case of mastectomy; not required in patients having undergone bilateral mastectomy); CT thorax and abdomen/pelvis with IV contrast. In case of any contra-indications (medical or regulatory): CT thorax without contrast + MRI abdomen/pelvis; Technetium-99m bone scintigraphy
3. Randomised trial: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
4. Randomised trial: Adequate organ function
5. Randomised trial: Women of childbearing potential (WOCBP) must have a negative highly sensitive serum or urine pregnancy test within 7 days prior to randomisation.
6. ctDNA screening phase: Intermediate to high risk of recurrence after definitive treatment for early breast cancer
7. ctDNA screening phase: Age ≥18 years
8. ctDNA screening phase: Patients must have received at least 1 year and up to 7.5 years of ET and planned to continue adjuvant ET during ctDNA screening phase
9. ctDNA screening phase: Previous neoadjuvant or adjuvant CDK4/6 inhibitor or PARP-inhibitor treatment is allowed provided it is completed
10. ctDNA screening phase: Available tumour sample from resected or biopsied tissue, with a tumour content of ≥20% (30% preferred) either before or after macro dissection (if performed) and a cell viability of a minimum 100 cells.
11. ctDNA screening phase: Written informed consent must be given according to ICH/GCP, and national/local regulations.
12. Randomised trial: ctDNA positive according to the Signatera ctDNA assay (main study ctDNA test) or other ctDNA assay approved for diagnostic purposes.
13. Randomised trial: Patients must receive adjuvant ET at the time of the ctDNA positive test
14. ctDNA screening phase: Invasive multicentric / multifocal disease is allowed provided that all the tested foci are ER+ HER2-. A sample from the highest-risk one, according to the investigator decision based on the size and grade, should be sent to Natera to build the patient ctDNA assay.
15. Randomised trial: Patients must meet the eligibility criteria for the screening phase, with the exception of the tissue sample requirements.

Exclusion criteria 16

1. ctDNA screening phase: Suspected recurrent disease or known conflicts with the inclusion and exclusion criteria for the randomised trial
2. ctDNA screening phase: Participation in another clinical study, with the exception of the SURVIVE study and observational (non-interventional) and non-drug intervention clinical studies. Note: patients participating in interventional studies may participate once they enter the follow-up period of the study
3. Randomised trial: Any unresolved toxic effect of prior therapies or surgical procedures of Grade ≥ 2 according to Common Terminology Criteria of Adverse Events (CTCAE) v5.0, with the exception of alopecia, peripheral neuropathy and other toxicities not considered a safety risk for the participant at investigator’s discretion
4. Randomised trial: Unable or unwilling to avoid over-the-counter medications, dietary/herbal supplements, and/or foods that are moderate/strong inhibitors or inducers of CYP3A4 activity
5. Randomised trial: Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications
6. ctDNA screening phase: Previous history of bone marrow and/or organ transplant
7. ctDNA screening phase: Blood transfusion within 3 months prior to registration or during the screening
8. Randomised trial: Any of the following cardiovascular disorders within 3 months before enrolment: myocardial infarction; stroke; severe/unstable angina; symptomatic cardiac arrhythmia; prolonged QTcF ≥ Grade 3 (i.e., > 500 msec); heart failure ≥ Class III as defined by the New York Heart Association (NYHA) guidelines
9. Randomised trial: Child-Pugh Score greater than Class A
10. Randomised trial: Uncontrolled significant active infections (≥ grade 3 according to CTCAE version 5), including active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency Virus (HIV)
11. Randomised trial: Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism
12. ctDNA screening phase: Prior treatment with any SERD or investigational ER antagonist
13. ctDNA screening phase: Previous history of invasive breast cancer
14. ctDNA screening phase: Previous history of any other malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
15. ctDNA screening phase: Bilateral invasive breast cancer
16. Randomised trial: CTCAE version 5.0 grade 3 or 4 dyslipidemia at the time of screening, defined as cholesterol>400 mg/dL or >10.34 mmol/L and/or triglycerides >500 mg/dL or >5.7 mmol/L.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Distant metastasis free survival (DMFS) defined as the time from randomisation until first distant metastatic recurrence or death from any cause, whichever occurs first

Secondary endpoints 5

1. Invasive disease-free survival (iDFS) rate according to the STEEP criteria including locoregional recurrence, distant metastasis, invasive contralateral breast cancer and invasive non-breast second cancers, deaths from any cause as events
2. Relapse-free survival (RFS) rate according to the STEEP criteria, including locoregional recurrence, distant metastasis, deaths from any cause as events
3. Overall survival rate
4. Safety including but not limited to all adverse events, serious adverse events, laboratory abnormalities graded according to CTCAE version 5.0
5. Patient reported outcomes: tolerability & benefit as measured by the QLQ-C30, QLQ-BR42 and EORTC IL46

Investigational products

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

Test 2

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83/11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 6

Locations

11 EU/EEA countries · 120 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 153 files

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

Application history

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