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

Official title

The T-REX-Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases; an Open, Multicenter, Randomized Non-inferiority Phase 3-trial.

Overview

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

Interventions

• Radiation De-escalation
  No regional radiotherapy. Radiotherapy is given to the remaining breast after breast conserving surgery. Chest wall radiotherapy after mastectomy only in case of wide spread multifocality.

Primary outcome measures

• Recurrence Free Survival [Time frame: Five years]

Secondary outcome measures (8)

• Locoregional recurrence [Time frame: Five years]
• Regional nodal recurrence [Time frame: Five years]
• New contralateral breast cancer [Time frame: Five years]
• Distant recurrence free survival [Time frame: Five years]
• Overall survival [Time frame: Five years]
• Arm morbidity [Time frame: Five years]
• Health-related quality of life [Time frame: Five years]
• Health-related quality of life [Time frame: Five years]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 18 centers

• Region Västragötaland — Borås
• Region Sörmland — Eskilstuna
• Region Gävleborg — Gävle
• Region Västra Götaland — Gothenburg
• Region Halland — Halmstad
• Region Jönköping — Jönköping
• Region Kalmar län — Kalmar
• Region Värmland — Karlstad
• … and 10 more centers

Norway · 9 centers

• Ålesund — Ålesund
• Bergen — Bergen
• Bodø — Bodø
• Gjövik — Gjøvik
• Kristiansand — Kristiansand
• Oslo — Oslo
• Stavanger — Stavanger
• Tromsø — Tromsø
• … and 1 more center

Finland · 3 centers

• Helsinki University Hospital — Helsinki
• Lahti Hospital — Lahti
• Turku University Hospital — Turku

Publications

• Alkner S, de Boniface J, Lundstedt D, Mjaaland I, Ryden L, Vikstrom J, Bendahl PO, Holmberg E, Sackey H, Wieslander E, Karlsson P. Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial. BMJ Open. 2023 Sep 26;13(9):e075543. d PMID 37751948

Identifiers

NCT: NCT05634889 · 2022-05093-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗