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

Breast Cancer Clinical Trial

— T-REX  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05634889
• Other study ID #: 2022-05093-02
• Status: Recruiting
• Phase: N/A
• Start date: March 17, 2023
• Est. completion date: December 31, 2033

Study information

• Verified date: August 2023
• Source: Region Skane
• Contact: Sara Alkner, Associate professor
• Phone: +4646171000
• Email: sara.alkner[@]med.lu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 in collaboration with Exact Sciences, and related to risk of recurrence and benefit of adjuvant radiotherapy.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1350
• Est. completion date: December 31, 2033
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Radiation:
• De-escalation
No regional radiotherapy. Radiotherapy towards the remaining breast after breast conserving surgery, but no radiotherapy at all after mastectomy.

Locations

Country	Name	City	State
Sweden	Region Västra Götaland	Gothenburg
Sweden	Region Jönköping	Jönköping
Sweden	Region Kalmar län	Kalmar
Sweden	Region Skåne	Lund
Sweden	Region Stockholm	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Region Skane	Exact Sciences Corporation

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Survival		Five years
Secondary	Locoregional recurrence		Five years
Secondary	Regional nodal recurrence		Five years
Secondary	New contralateral breast cancer		Five years
Secondary	Distant recurrence free survival		Five years
Secondary	Overall survival		Five years
Secondary	Arm morbidity	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.	Five years
Secondary	Health-related quality of life	Assessed by the questionnaire EORTC QLQ-C-30 completed by study participants between randomization and RT, and after 1, 3, and 5 years.	Five years
Secondary	Health-related quality of life	Assessed by the questionnaire BR-23 completed by study participants between randomization and RT, and after 1, 3, and 5 years.	Five years