TREAT ctDNA Elacestrant

This is an interventional treatment trial for ER-positive Breast Cancer Read More

Inclusion Criteria:

• ctDNA screening phase

  • Female 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
    • 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

  • Elevated risk of recurrence after definitive treatment for early breast cancer, defined as either:

    • Stage IIB or stage III disease according to the 8th edition of the UICC TNM classification and completion of adjuvant chemotherapy, OR
    • Completion of at least 4 cycles of neoadjuvant chemotherapy and residual tumour at surgery of ≥ 1cm (≥ypT1c) or axillary node + (ypN+)
  • Pre- or postmenopausal status (for female patients).
  • Age ≥18 years
  • Patients must have received at least 2 years and up to 7 years of ET
  • Previous adjuvant CDK4/6 inhibitor or PARP-inhibitor treatment is allowed if completed at least 12 months before registration
  • Patients with multifocal tumours are allowed provided all foci are biopsied and are ER-positive and HER2-negative as defined above
  • Available FFPE tumour block from the baseline biopsy or from surgical specimen or at least 10 slides of 10μm and a tumour cellularity of at least 25%. For patients with multifocal tumours, FFPE block or slides from the largest focus is required.
  • Written informed consent must be given according to ICH/GCP, and national/local regulations.

• Randomised phase

  • ctDNA positive according to the RaDaR assay

  • Absence of locoregional and/or metastatic disease, 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
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Adequate organ function
  • Women of childbearing potential (WOCBP) must have a negative highly sensitive serum or urine pregnancy test within 3 days prior to randomisation.

Exclusion Criteria:

• ctDNA screening phase

  • Suspected recurrent disease or known conflicts with the inclusion and exclusion criteria for the randomised trial
  • Prior treatment with any SERD or investigational ER antagonist
  • Previous history of invasive breast cancer
  • 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 of the cervix . Patients who have been disease free for more than 5 years with low risk of relapse are allowed
  • Bilateral breast cancer
  • Participation in another clinical study, with the exception of the SURVIVE study Note: patients participating in interventional studies may participate once they enter the follow-up period of the study

• Randomised phase

  • 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
  • Unable or unwilling to avoid prescription medications, over-the-counter medications, dietary/herbal supplements, and/or foods that are moderate/strong inhibitors or inducers of CYP3A4 activity
  • Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications
  • Any of the following cardiovascular disorders within 3 months before enrolment:
  • Child-Pugh Score greater than Class A
  • 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)
  • Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism