NCT07084558

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

ABCSG 61 / TEODOR (Neoadjuvant TrEatment Optimization Driven by ctDNA and endOcrine Responsiveness): A Prospective, Randomized, Controlled, Openlabel Multicenter Phase II Study Investigating Neoadjuvant Endocrine Therapy Versus Chemotherapy in HR-positive, HER2negative, ctDNA-negative and Endocrine Responsive Early and Locally Advanced Breast Cancer

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 350 (estimated)
• Sponsor: Austrian Breast & Colorectal Cancer Study Group · Network
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	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
DIAGNOSTIC_TEST	biopsy for Ki-67 assessment	Ki67: Evaluation of Ki-67-value after 3 weeks of aromatase inhibitor
DIAGNOSTIC_TEST	FFPE tumor sample for Signatera (TM) test (archived)	Evaluation of ctDNA status prior to treatment start

Timeline

• Start date: 2025-08-13
• Primary completion: 2028-06-30
• Completion: 2033-06-30
• First posted: 2025-07-24
• Last updated: 2025-10-28

Locations

14 sites across 1 country: Austria

Regulatory

• FDA-regulated device study