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

NCT07084558 | Recruiting DMC FDA Device

• 1 other identifier: ABCSG 61 / TEODOR
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 14

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

Conditions

Early and Locally Advanced Breast Cancer

Keywords

early breast cancer; locally advanced breast cancer; neoadjuvant endocrine therapy; chemotherapy; HR-positive; HER2-negative; ABCSG 61; TEODOR; endocrine responsive; Natera; in-vitro diagnostic; Signatera Test; Signatera; ctDNA

Outcome Measures

Primary Outcomes (1)

• Modified PEPI (Preoperative Endocrine Prognostic Index) score

  The proportions of patients with a modified PEPI score of 0 are compared between treatment arm A and treatment arm B. The score ranges between 0 and 12 with 0 indicating the lowest risk of relapse.

  From randomization to the timepoint of surgery

Secondary Outcomes (7)

• RCB (Residual Cancer Burden) score

  From randomization to the timepoint of surgery

• BCTOR (Breast Conservation Turn-Over Rate)

  From randomization to the timepoint of surgery

• EFS (Event-Free Survival)

  From randomization until the end of the 5-year follow-up post-surgery period

• iDFS (Invasive Disease-Free Survival )

  From primary surgery until the end of the 5-year follow-up post-surgery period

• iBCFS (Invasive Breast Cancer-Free Survival )

  From primary surgery until the end of the 5-year follow-up post-surgery period

Study Arms (3)

Endocrine treatment for responders to treatment with aromatase inhibitor

EXPERIMENTAL

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

Diagnostic Test: blood sample for Signatera (TM) test; Diagnostic Test: biopsy for Ki-67 assessment; Diagnostic Test: FFPE tumor sample for Signatera (TM) test (archived)

Chemotherapy for responders to treatment with aromatase inhibitor

EXPERIMENTAL

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

Diagnostic Test: blood sample for Signatera (TM) test; Diagnostic Test: biopsy for Ki-67 assessment; Diagnostic Test: FFPE tumor sample for Signatera (TM) test (archived)

Chemotherapy for non-responders to treatment with aromatase inhibitor

EXPERIMENTAL

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

Diagnostic Test: blood sample for Signatera (TM) test; Diagnostic Test: biopsy for Ki-67 assessment; Diagnostic Test: FFPE tumor sample for Signatera (TM) test (archived)

Interventions

blood sample for Signatera (TM) test 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

Chemotherapy for non-responders to treatment with aromatase inhibitor; Chemotherapy for responders to treatment with aromatase inhibitor; Endocrine treatment for responders to treatment with aromatase inhibitor

biopsy for Ki-67 assessment DIAGNOSTIC_TEST

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

Chemotherapy for non-responders to treatment with aromatase inhibitor; Chemotherapy for responders to treatment with aromatase inhibitor; Endocrine treatment for responders to treatment with aromatase inhibitor

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

Evaluation of ctDNA status prior to treatment start

Chemotherapy for non-responders to treatment with aromatase inhibitor; Chemotherapy for responders to treatment with aromatase inhibitor; Endocrine treatment for responders to treatment with aromatase inhibitor

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent obtained prior to any study specific assessments and procedures
• Women and men of age ≥18 years
• 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
• Systemic chemotherapy indicated by multidisciplinary tumor board
• Absence of prior breast cancer specific treatment for the current malignancy when entering screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate bone marrow and organ function as defined by the following local laboratory values within 8 weeks before study treatment start:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 10.0 g/dL
• Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m² for patients with serum creatinine levels above institutional ULN.

You may not qualify if:

• Ineligible for appropriate locoregional treatment (breast surgery and or radiotherapy when indicated)
• Bilateral invasive breast cancer or synchronous DCIS in contralateral breast
• 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.
• Any chronic medication contraindicated for antineoplastic treatment
• 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
• \) 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.).
• \) 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

Sponsors & Collaborators

• Austrian Breast & Colorectal Cancer Study Group: lead
• Natera, Inc.: collaborator

Study Sites (14)

Allg. Gynäkologie u. gyn. Onkologie/Senologie

Vienna, Austria, 1190, Austria

RECRUITING

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

Baden, Austria

ACTIVE NOT RECRUITING

Dornbirn BGZ; Frauenheilkunde u. Geburtshilfe

Dornbirn, Austria

ACTIVE NOT RECRUITING

Landeskrankenhaus Feldkirch Interne E

Feldkirch, Austria

ACTIVE NOT RECRUITING

MUG - LKH Graz Klin. Abt. f. Onkologie

Graz, Austria

ACTIVE NOT RECRUITING

MUG - Univ. Frauenklinik Graz, Gyn. Abteilung

Graz, Austria

ACTIVE NOT RECRUITING

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

Innsbruck, Austria

RECRUITING

TumorZentrum Kepler Universitätsklinikum Linz

Linz, Austria

ACTIVE NOT RECRUITING

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

Salzburg, Austria

NOT YET RECRUITING

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

Sankt Pölten, Austria

ACTIVE NOT RECRUITING

KH BHB St. Veit/Glan Brustzentrum Kärnten

Sankt Veit an der Glan, Austria

ACTIVE NOT RECRUITING

Hanusch Krankenhaus, 3. Medizinische Abteilung

Vienna, Austria

ACTIVE NOT RECRUITING

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

Vienna, Austria

ACTIVE NOT RECRUITING

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

Wiener Neustadt, Austria

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Blood Specimen Collection; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Daniel Egle, MD, senior physician

  Medical University Innsbruck

  STUDY CHAIR

• Michael Gnant, MD, Prof.

  Medical University Vienna, CCC

  STUDY CHAIR

Central Study Contacts

Katharina Jarolim, PhD

CONTACT

+43 1 4089230; katharina.jarolim@abcsg.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: July 24, 2025
• Study Start: August 13, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2033
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

AU (14)