The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases.

Not Applicable

Recruiting

• Conditions: Breast Cancer
• Interventions: Radiation: De-escalation

• Registration Number: NCT05634889
• Lead Sponsor: Region Skane

Brief Summary

T-REX is a randomized multicenter, non-inferiority trial.

Aim: To evaluate whether regional radiotherapy may safely be omitted in clinically node negative breast cancer patients with one or two sentinel node macrometastases and an estrogen receptor positive, HER2-negative tumor. Leading to an improved quality of life and reduced side effects, without worsening recurrence free survival at five years.

Intervention: Patients will be randomized to locoregional radiotherapy towards the breast/chestwall and regional lymph nodes vs. to a de-escalated radiotherapy.

In the intervention arm no lymph node irradiation will be given. Radiotherapy is still given to the remaining breast after breast conserving surgery, but no radiotherapy is given after mastectomy.

Sample size: 1350 patients

Primary end-point: Recurrence free survival at five years.

Gene expression analysis: For all patients gene expression analysis for the gene signatures ARTIC, POLAR and OncotypeDX will be performed and related to risk of recurrence and benefit of adjuvant radiotherapy.

Detailed Description

In this multicenter, prospective randomized trial clinically node-negative breast cancer patients with 1-2 macrometastases in their sentinel lymph node biopsy, and an estrogen receptor positive, HER2-negative tumor, will be randomly assigned to either receive adjuvant locoregional radiotherapy, or no regional radiotherapy.

The main aim is to evaluate whether regional radiotherapy may safely be omitted in patients with limited lymph node metastasis and an estimated low risk of locoregional recurrence. Recurrence free survival after five years is the primary outcome, which for non-inferiority should not worsen more than 4.5 percentage units. Secondary outcomes are locoregional recurrence, regional nodal recurrence, new contralateral BC, distant recurrence free survival, overall survival, non-breast malignancies, cardiac disease, arm morbidity, and health-related quality of life.

Target volumes include:

Standard arm - The remaining breast/chest wall, axillary lymph node levels I-III, the supraclavicular lymph nodes (level IV), the interpectoral lymph nodes and in patients with a medial/central tumor also the internal mammary lymph nodes.

Intervention arm - The remaining breast after breast conserving surgery. No radiotherapy after mastectomy

Study Timeline

• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-11-29
• Study First Posted: 2022-12-02
• Study Start: 2023-03-17
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-17
• Last Update Posted: 2024-11-20
• Primary Completion: 2028-12-31
• Study Completion: 2033-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1350

Inclusion Criteria

1. Primary unifocal or multifocal invasive breast cancer T1-T2.
2. Clinically N0.
3. Macrometastasis (>2mm) in 1-2 lymph nodes at sentinel node biopsy.
4. Oral and written consent.
5. Age ≥ 18 years.
6. All resection margins are tumor free (no tumor on ink).
7. Primary tumor ER-positive, HER2-negative.

Exclusion Criteria

1. Regional or distant metastases outside the ipsilateral axilla.
2. Previous RT towards the planned target area, i.e. the ipsilateral chest/lymph nodes.
3. Neoadjuvant systemic therapy.
4. Axillary lymph node dissection or other previous axillary surgery on the affected side.
5. Prior history of invasive breast cancer.
6. Pregnancy.
7. Bilateral invasive breast cancer.
8. Contraindication for radiotherapy or systemic treatment.
9. Inability to absorb or understand the contents of the informed consent form; for example, through disability, inadequate language skills or dementia.
10. Other invasive cancer within 5 years prior to breast cancer diagnosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	De-escalation	No regional radiotherapy. Radiotherapy is given to the remaining breast after breast conserving surgery, while mastectomy patients do not receive any radiotherapy at all.

Primary Outcome Measures

Name	Time	Method
Recurrence Free Survival	Five years

Secondary Outcome Measures

Name	Time	Method
Locoregional recurrence	Five years
Distant recurrence free survival	Five years
New contralateral breast cancer	Five years
Arm morbidity	Five years	Assessed by questionnaires completed by study participants digitally or on paper between randomization and start of RT, and after 1, 3, and 5 years. The questionnaire used is the Lymphedema Functioning, Disability and Health Questionnaire (Lymph-ICF) developed by Devoogdt in 2011.
Regional nodal recurrence	Five years
Overall survival	Five years
Health-related quality of life	Five years	Assessed by the questionnaire BR-23 completed by study participants between randomization and RT, and after 1, 3, and 5 years.

Trial Locations

Locations (25)

Bergen; 🇳🇴 Bergen, Norway

Bodø; 🇳🇴 Bodø, Norway

Gjövik; 🇳🇴 Gjövik, Norway

Kristiansand; 🇳🇴 Kristiansand, Norway

Oslo; 🇳🇴 Oslo, Norway

Stavanger; 🇳🇴 Stavanger, Norway

Tromsø; 🇳🇴 Tromsø, Norway

Trondheim; 🇳🇴 Trondheim, Norway

Ålesund; 🇳🇴 Ålesund, Norway

Region Västragötaland; 🇸🇪 Skövde, Sweden

Region Gävleborg; 🇸🇪 Gävle, Sweden

Region Halland; 🇸🇪 Halmstad, Sweden

Region Värmland; 🇸🇪 Karlstad, Sweden

Region Östergötland; 🇸🇪 Linköping, Sweden

Region Västernorrland; 🇸🇪 Sundsvall, Sweden

Region Västerbotten; 🇸🇪 Umeå, Sweden

Region Uppsala; 🇸🇪 Uppsala, Sweden

Region Västmanland; 🇸🇪 Västerås, Sweden

Region Kronoberg; 🇸🇪 Växjö, Sweden

Region Örebro; 🇸🇪 Örebro, Sweden

Region Västra Götaland; 🇸🇪 Gothenburg, Sweden

Region Jönköping; 🇸🇪 Jönköping, Sweden

Region Kalmar län; 🇸🇪 Kalmar, Sweden

Region Skåne; 🇸🇪 Lund, Sweden

Region Stockholm; 🇸🇪 Stockholm, Sweden