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

Официальное название

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.

Обзор

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.

Подробное описание

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

Вмешательства

• Лучевая терапия 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.

Первичные конечные точки

• Recurrence Free Survival [Срок оценки: Five years]

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швеция · 18 центров

• 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
• … и ещё 10 центров

Норвегия · 9 центров

• Ålesund — Ålesund
• Bergen — Bergen
• Bodø — Bodø
• Gjövik — Gjøvik
• Kristiansand — Kristiansand
• Oslo — Oslo
• Stavanger — Stavanger
• Tromsø — Tromsø
• … и ещё 1 центр

Финляндия · 3 центра

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

Публикации

• 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

Идентификаторы

NCT: NCT05634889 · 2022-05093-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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