TREAT ctDNA Elacestrant
Primary Purpose
ER-positive Breast Cancer, HER2-negative Breast Cancer, Stage IIB Breast Cancer
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Elacestrant
Tamoxifen
Letrozole 2.5mg
Anastrozole 1mg
Exemestane 25 MG
Sponsored by
About this trial
This is an interventional treatment trial for ER-positive Breast Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental arm
Control arm
Arm Description
elacestrant 400 mg/day orally once daily on a continuous dosing schedule
standard endocrine treatment - the same they were receiving at the time of ctDNA detection
Outcomes
Primary Outcome Measures
Distant metastasis free survival (DMFS)
DMFS defined as the time from randomisation until first distant metastatic recurrence or death from any cause, whichever occurs first
Secondary Outcome Measures
ctDNA elimination rate at month 1
defined as the proportion of randomised patients who had a negative ctDNA test result at month 1
Full Information
NCT ID
NCT05512364
First Posted
August 22, 2022
Last Updated
August 22, 2022
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Breast International Group, Menarini Group
1. Study Identification
Unique Protocol Identification Number
NCT05512364
Brief Title
TREAT ctDNA Elacestrant
Official Title
Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 1, 2023 (Anticipated)
Primary Completion Date
July 1, 2028 (Anticipated)
Study Completion Date
May 1, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Breast International Group, Menarini Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an international, multi-center, randomised, open label, superiority phase III trial of elacestrant vs standard endocrine therapy in patients with ER+/HER2- breast cancer and ctDNA relapse.
During the ctDNA screening phase, patients will be tested at different timepoints to detect the presence of ctDNA in their blood.
Patients who are found to be ctDNA-positive and have no evidence of distant metastasis, will be randomised 1:1 between standard endocrine treatment (the same they were receiving when tested ctDNA positive) versus elacestrant, provided they meet all eligibility criteria. After completion of the protocol treatment period, treatment will be left at the discretion of the treating physician.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ER-positive Breast Cancer, HER2-negative Breast Cancer, Stage IIB Breast Cancer, Stage III Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
220 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental arm
Arm Type
Experimental
Arm Description
elacestrant 400 mg/day orally once daily on a continuous dosing schedule
Arm Title
Control arm
Arm Type
Active Comparator
Arm Description
standard endocrine treatment - the same they were receiving at the time of ctDNA detection
Intervention Type
Drug
Intervention Name(s)
Elacestrant
Intervention Description
400mg QD orally on a continuous dosing schedule
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
20 mg QD orally on a continuous dosing schedule
Intervention Type
Drug
Intervention Name(s)
Letrozole 2.5mg
Intervention Description
2.5 mg QD orally on a continuous dosing schedule
Intervention Type
Drug
Intervention Name(s)
Anastrozole 1mg
Intervention Description
1 mg QD orally on a continuous dosing schedule
Intervention Type
Drug
Intervention Name(s)
Exemestane 25 MG
Intervention Description
25 mg QD orally on a continuous dosing schedule
Primary Outcome Measure Information:
Title
Distant metastasis free survival (DMFS)
Description
DMFS defined as the time from randomisation until first distant metastatic recurrence or death from any cause, whichever occurs first
Time Frame
5.2 years after first patient screened
Secondary Outcome Measure Information:
Title
ctDNA elimination rate at month 1
Description
defined as the proportion of randomised patients who had a negative ctDNA test result at month 1
Time Frame
at month 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
EORTC HQ
Phone
+32 2 774 16 11
Email
eortc@eortc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michail Ignatiadis
Organizational Affiliation
Institut Jules Bordet, Belgium
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Emmanouil Saloustros
Organizational Affiliation
General University Hospital of Larissa, Greece
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
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TREAT ctDNA Elacestrant
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