ABCSG 61 / TEODOR : Neoadjuvant TrEatment Optimization Driven by Circulating Tumor DNA and endOcrine Responsiveness

NCT ID: NCT07084558

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-13
• Study Completion Date: 2033-06-30

Brief Summary

The goal of this performance study is to learn if treatment with neoadjuvant endocrine therapy compared to chemotherapy has comparable efficacy, but better quality of life outcomes in endocrine responsive participants with early and locally advanced ER+/HER2-negative breast cancer and no detectable ctDNA in peripheral blood.

The main question it aims to answer is:

Is neoadjuvant endocrine therapy at least equivalent to neoadjuvant chemotherapy for treatment of patients with ER-positive, HER2-negative breast cancer with no detectable ctDNA (as assessed with the SignateraTM test) prior to treatment start and a Ki-67-value smaller or equal to 10% after 3 weeks of initial aromatase inhibitor treatment (=endocrine responsive).

Researchers will compare neoadjuvant Standard of Care aromatase inhibitors (AI) or tamoxifen, if AI is not tolerated, with neoadjuvant Standard of Care chemotherapy to see if treatment efficacy is at least comparable between the treatment arms, when measured with the modified preoperative endocrine prognostic index (PEPI) score at surgery.

Participants will:

• Provide blood and tumor samples for ctDNA-assessment with the SignateraTM test by Natera prior to treatment starts
• Take AI therapy for 4 weeks in the initial Run-in phase
• Undergo tumor biopsy after 3 weeks of AI for local evaluation of Ki-67
• Receive either 8 months of neoadjuvant Standard of Care AI/ tamoxifen or 6-8 months of neoadjuvant Standard of Care chemotherapy in one of the three treatment arms of the Main Treatment Phase, depending on SignateraTM test result and Ki-67 value after 3 weeks of AI therapy (see "detailed description" for details).
• Visit the clinic for checkups and tests at timepoints:

• Prior to starting trial treatment
• 3 weeks after start of endocrine treatment in the Run-in phase
• Approx. 1 week later, prior to start of Main Treatment
• After half of the therapy in the Main Therapy Phase has been completed
• Once Main Treatment Phase treatment is complete (after 7-9 months overall)
• For surgery and post-surgery checkup
• Annually during the 5 years follow-up phase after surgery.
• A subset of patients, who receive adjuvant chemotherapy after surgery, are asked to come to site for an additional visit after completion of chemotherapy.
• Provide blood samples for ctDNA-assessment and future research when visiting the clinic
• Answer patient-reported questionnaires about their quality of life, symptoms and sexual health

Detailed Description

This is a prospective, randomized, controlled, open-label phase II performance study for participants with ER+/ HER2- early or locally advanced breast cancer. At the start of the trial, ctDNA is assessed for all participants with the SignateraTM test by Natera, using (archived) tumor tissue and blood samples. Eligible patients start AI therapy per Standard of Care in the Run-in Phase and after 3 weeks of treatment, Ki-67 levels are measured locally, to determine endocrine response. Following the Run-in Phase, participants, whose SignateraTM test result shows no detectable ctDNA and whose Ki-67 value is ≤ 10% are randomized 2:1 to receive either neoadjuvant AI or, if AI is not tolerated, tamoxifen in arm A or neoadjuvant chemotherapy in arm B. Participants with a Ki-67 value of >10% or detectable ctDNA, according to the SignateraTM test, receive chemotherapy in the third treatment arm C. All study treatment is applied as per standard of care. The planned duration of treatment is 4 weeks in the Run-in phase and 6-8 months in either arm of the Main Treatment Phase. The primary endpoint is the modified PEPI score. Patients will be followed for 5 years from surgery.

Conditions

Early and Locally Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Endocrine treatment for responders to treatment with aromatase inhibitor

Patients are considered responders if they are ctDNA-negative prior treatment and if Ki-67 is less than or equal to 10% after 3 weeks of treatment with aromatase inhibitor

Group Type: EXPERIMENTAL

blood sample for Signatera (TM) test

Intervention Type: DIAGNOSTIC_TEST

ctDNA: Evaluation of ctDNA-status prior to treatment start (ctDNA not detected or ctDNA-positive) until the last of five follow-up visit

biopsy for Ki-67 assessment

Intervention Type: DIAGNOSTIC_TEST

Ki67: Evaluation of Ki-67-value after 3 weeks of aromatase inhibitor

FFPE tumor sample for Signatera (TM) test (archived)

Intervention Type: DIAGNOSTIC_TEST

Evaluation of ctDNA status prior to treatment start

Chemotherapy for responders to treatment with aromatase inhibitor

Patients are considered responders if they are ctDNA-negative prior treatment and if Ki-67 is less than or equal to 10% after 3 weeks of treatment with aromatase inhibitor

Group Type: EXPERIMENTAL

blood sample for Signatera (TM) test

Intervention Type: DIAGNOSTIC_TEST

ctDNA: Evaluation of ctDNA-status prior to treatment start (ctDNA not detected or ctDNA-positive) until the last of five follow-up visit

biopsy for Ki-67 assessment

Intervention Type: DIAGNOSTIC_TEST

Ki67: Evaluation of Ki-67-value after 3 weeks of aromatase inhibitor

FFPE tumor sample for Signatera (TM) test (archived)

Intervention Type: DIAGNOSTIC_TEST

Evaluation of ctDNA status prior to treatment start

Chemotherapy for non-responders to treatment with aromatase inhibitor

Patients are considered non-responders if they are ctDNA-positive prior treatment and if Ki-67 is greater than 10% after 3 weeks of treatment with aromatase inhibitor

Group Type: EXPERIMENTAL

blood sample for Signatera (TM) test

Intervention Type: DIAGNOSTIC_TEST

ctDNA: Evaluation of ctDNA-status prior to treatment start (ctDNA not detected or ctDNA-positive) until the last of five follow-up visit

biopsy for Ki-67 assessment

Intervention Type: DIAGNOSTIC_TEST

Ki67: Evaluation of Ki-67-value after 3 weeks of aromatase inhibitor

FFPE tumor sample for Signatera (TM) test (archived)

Intervention Type: DIAGNOSTIC_TEST

Evaluation of ctDNA status prior to treatment start

Interventions

blood sample for Signatera (TM) test

ctDNA: Evaluation of ctDNA-status prior to treatment start (ctDNA not detected or ctDNA-positive) until the last of five follow-up visit

Intervention Type: DIAGNOSTIC_TEST

biopsy for Ki-67 assessment

Ki67: Evaluation of Ki-67-value after 3 weeks of aromatase inhibitor

Intervention Type: DIAGNOSTIC_TEST

FFPE tumor sample for Signatera (TM) test (archived)

Evaluation of ctDNA status prior to treatment start

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent obtained prior to any study specific assessments and procedures

2. Women and men of age ≥18 years

3. Patients must have histologically confirmed invasive, unilateral and locally advanced breast cancer with the following characteristics:

• Stage IIA-III per AJCC (American Joint Committee on Cancer) Breast Cancer Staging version 8
• Histologically confirmed hormone receptor positive and HER2 negative tumor(s); HER2 measurement to be assessed locally according to the ASCO/CAP guidelines. In case the tumor is multicentric and/or multifocal, all histopathologically examined tumors must meet the pathologic criteria for hormone receptor positive and HER2 negative
• ER positive tumors, i.e. >20% positive stained tumor cells
• PR positive or negative tumors

4. Systemic chemotherapy indicated by multidisciplinary tumor board

5. Absence of prior breast cancer specific treatment for the current malignancy when entering screening

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Adequate bone marrow and organ function as defined by the following local laboratory values within 8 weeks before study treatment start:

1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

2. Platelets ≥ 100 × 109/L

3. Hemoglobin ≥ 10.0 g/dL

4. Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m² for patients with serum creatinine levels above institutional ULN.

5. Alanine amino transferase (ALT or SGPT) ≤ 1.5 × Upper Limit Normal (ULN); Aspartate amino transferase (AST or SGOT) ≤ 1.5 × ULN f. Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome

8. Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.

9. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

10. In women of childbearing potential, urine or serum pregnancy test must be negative within 28 days prior to registration. In postmenopausal women or hysterectomized patients, pregnancy tests do not need to be performed

Exclusion Criteria

1. Ineligible for appropriate locoregional treatment (breast surgery and or radiotherapy when indicated)

2. Bilateral invasive breast cancer or synchronous DCIS in contralateral breast

3. Patients receiving concurrent systemic exogenous sexual hormone therapy during the study (hormone replacement therapy, oral or any other hormonal contraceptives such as hormonal contraceptive coil, etc.) are not eligible but topical vaginal estrogen therapy is allowable.

4. Any chronic medication contraindicated for antineoplastic treatment

5. Participation in a prior or concurrent interventional study and receiving study treatment (concurrent or within 30 days prior to treatment start) 6) Patients receiving any prior systemic cancer therapy for invasive breast cancer

7) Patients with a history of any malignancy are ineligible except for the following circumstances:

• Patients with a malignancy history other than adequately treated invasive breast cancer are eligible if they have been disease-free for at least 2 years and are deemed by the investigator to be at very low risk for recurrence of that malignancy (e.g. stage I gastric cancer or skin cancer)
• Patients with the following cancers are eligible, even if diagnosed and adequately treated within the past 2 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and non-metastatic nonmelanomatous skin cancers 8) Patient has medical or psychiatric disorders that would, in the investigator's judgement, interfere with the patient's safety or informed consent (e.g. known uncontrolled HIV infection, chronic/active viral or other known hepatitis and/or chronic liver disease, cirrhosis etc.).

9) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation 10) Patient has current impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the oral study treatments (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection) 11) Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator´s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol or limit life expectancy to ≤5 years 12) Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during study treatment and 6 months thereafter

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Natera, Inc.

INDUSTRY

Sponsor Role: collaborator

Austrian Breast & Colorectal Cancer Study Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Egle, MD, senior physician

Role: STUDY_CHAIR

Medical University Innsbruck

Michael Gnant, MD, Prof.

Role: STUDY_CHAIR

Medical University Vienna, CCC

Locations

Allg. Gynäkologie u. gyn. Onkologie/Senologie

Vienna, Austria, Austria

Site Status: RECRUITING

Landesklinikum Baden BGZ; Abt. f. Allgemein- u. Viszeralchirurgie

Baden, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Dornbirn BGZ; Frauenheilkunde u. Geburtshilfe

Dornbirn, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Landeskrankenhaus Feldkirch Interne E

Feldkirch, , Austria

Site Status: ACTIVE_NOT_RECRUITING

MUG - LKH Graz Klin. Abt. f. Onkologie

Graz, , Austria

Site Status: ACTIVE_NOT_RECRUITING

MUG - Univ. Frauenklinik Graz, Gyn. Abteilung

Graz, , Austria

Site Status: ACTIVE_NOT_RECRUITING

MUI - Univ. Klinik f. Frauenheilkunde Innsbruck Klin. Abteilung f. Gynäkologie u. Geburtshilfe

Innsbruck, , Austria

Site Status: RECRUITING

TumorZentrum Kepler Universitätsklinikum Linz

Linz, , Austria

Site Status: ACTIVE_NOT_RECRUITING

LKH Salzburg - PMU, Univ.Klinik f. Innere Medizin III / SCRI CCCIT

Salzburg, , Austria

Site Status: NOT_YET_RECRUITING

Universitätsklinikum St. Pölten, Klin. Abteilung f. Innere Medizin 1

Sankt Pölten, , Austria

Site Status: ACTIVE_NOT_RECRUITING

KH BHB St. Veit/Glan Brustzentrum Kärnten

Sankt Veit an der Glan, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Hanusch Krankenhaus, 3. Medizinische Abteilung

Vienna, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Klinik Hietzing, Gyn. Abteilung; Karl Landsteiner Institut f. gyn. Onkologie u. Senologie

Vienna, , Austria

Site Status: ACTIVE_NOT_RECRUITING

Universitätsklinikum Wiener Neustadt, Abteilung für Innere Medizin, Hämatologie und int. Onkologie

Wiener Neustadt, , Austria

Site Status: NOT_YET_RECRUITING

Countries

Austria

Central Contacts

Katharina Jarolim, PhD

Role: CONTACT

katharina.jarolim@abcsg.at

+43 1 4089230

Facility Contacts

Sabine Danzinger

Role: primary

sabine.danzinger@meduniwien.ac.at

+43140400

Daniel Egle

Role: primary

daniel.egle@tirol-kliniken.at

+4350504230

Simon Peter Gampenrieder

Role: primary

s.gampenrieder@salk.at

+43572550

Mira Witek

Role: primary

mirasofie.witek@wienerneustadt.lknoe.at

+43262290040

Other Identifiers

ABCSG 61 / TEODOR

Identifier Type: -

Identifier Source: org_study_id