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

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

Interventions

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

Sponsors & Collaborators

• Natera, Inc.

  collaborator INDUSTRY

• Austrian Breast & Colorectal Cancer Study Group

  lead NETWORK

Principal Investigators

• Daniel Egle, MD, senior physician · Medical University Innsbruck

• Michael Gnant, MD, Prof. · Medical University Vienna, CCC

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-13

Primary Completion

2028-06-30

Completion

2033-06-30

FDA Device

Yes

Countries

• Austria

Study Locations