Clinical trial NCT05634889: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
radiotherapy
gene expression analysis
adjuvant breast cancer treatment
regional breast cancer treatment
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Exact Sciences Corporation
First posted: 2022-12-02
Enrollment: 1350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Recurrence Free Survival
timeFrame: Five years
Secondary outcomes:
measure: Locoregional recurrence
timeFrame: Five years
measure: Regional nodal recurrence
timeFrame: Five years
measure: New contralateral breast cancer
timeFrame: Five years
measure: Distant recurrence free survival
timeFrame: Five years
measure: Overall survival
timeFrame: Five years
measure: Arm morbidity
timeFrame: Five years
measure: Health-related quality of life
timeFrame: Five years
measure: Health-related quality of life
timeFrame: Five years
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Bergen
city: Bodø
country: Norway
facility: Bodø
city: Gjövik
country: Norway
facility: Gjövik
city: Kristiansand
country: Norway
facility: Kristiansand
city: Oslo
country: Norway
facility: Oslo
city: Stavanger
country: Norway
facility: Stavanger
city: Tromsø
country: Norway
facility: Tromsø
city: Trondheim
country: Norway
facility: Trondheim
city: Ålesund
country: Norway
facility: Ålesund
city: Borås
country: Sweden
facility: Region Västragötaland
city: Gothenburg
country: Sweden
facility: Region Västra Götaland
city: Gävle
country: Sweden
facility: Region Gävleborg
city: Halmstad
country: Sweden
facility: Region Halland
city: Jönköping
country: Sweden
facility: Region Jönköping
city: Kalmar
country: Sweden
facility: Region Kalmar län
city: Karlstad
country: Sweden
facility: Region Värmland
city: Linköping
country: Sweden
facility: Region Östergötland
city: Lund
country: Sweden
facility: Region Skåne
city: Skövde
country: Sweden
facility: Region Västragötaland
city: Stockholm
country: Sweden
facility: Region Stockholm
city: Sundsvall
country: Sweden
facility: Region Västernorrland
city: Umeå
country: Sweden
facility: Region Västerbotten
city: Uppsala
country: Sweden
facility: Region Uppsala
city: Västerås
country: Sweden
facility: Region Västmanland
city: Växjö
country: Sweden
facility: Region Kronoberg
city: Örebro
country: Sweden
facility: Region Örebro
Study officials:
affiliation: Lunds Universitet
name: Sara Alkner, Associate professor
role: PRINCIPAL_INVESTIGATOR
References: