Clinical trial NCT04281355: Individualized Locoregional Treatment of Initially Biopsy-proven Node-positive Breast Cancer After Primary Systemic Therapy
Official title: Individualized Locoregional Treatment of Initially Biopsy-proven Node-positive Breast Cancer After Primary Systemic Therapy: The EUBREAST-2 INDAX Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2020-02-24
Enrollment: 0
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: In clinically node-positive (cN+) breast cancer, preoperative systemic therapy (PST) is common. With increasing rates of complete tumour eradication, there is a need for de-escalation of locoregional treatment in the interest of decreased morbidity.

In order to individually adapt postoperative therapies, axillary staging is crucial. Axillary lymph node dissection (ALND) comes at a high risk of arm morbidity. There is extreme divergence in the use of less extensive staging methods, i.e. targeted lymph node biopsy (TLNB), sentinel node biopsy (SNB) or both (TAD), and in the use of subsequent locoregional treatment, since prospective data are largely lacking.

The main purpose of the European INDAX trial is to implement de-escalated staging and evaluate which regional treatment, individually adapted to the response after PST, is oncologically safe but least harmful.

Population: cN+ breast cancer patients receiving PST, recruited 2021-2025. Staging by TLNB, TAD or SNB.

Intervention: Negative staging (ypN0, Randomisation A, N=1433): no regional treatment. Positive staging (ypN+, Randomisation B, N=1513): no ALND but regional radiotherapy (rRT).

Control: Randomisation A: rRT only. Randomisation B: ALND plus rRT.

Outcome: Invasive disease-free survival (non-inferiority), arm morbidity and quality of life.

Drug tests in whole-tumour organoid cultures, algorithm-based digital image analysis and gene expression analysis are performed to improve response prediction, facilitate tailoring of PST and increase eradication rates.


Eligibility criteria: Inclusion Criteria:

* Patients with primary invasive breast cancer cT1-cT3
* cN1 status prior to PST
* Cytological or histological proof of axillary metastasis before PST
* Full tumour biology available before initiation of PST
* Oral and written consent
* Age ≥ 18 years

Exclusion Criteria:

* Biopsy-confirmed regional nodal metastases outside of the ipsilateral axilla
* Distant metastases at diagnosis
* Inflammatory breast cancer
* Previous axillary surgery
* Previous radiotherapy to ipsilateral breast, chest or axilla
* History of prior invasive breast cancer
* Ongoing pregnancy or breast-feeding
* Bilateral invasive breast cancer
* Medical contraindication for radiotherapy or inability to receive recommended radiotherapy
* Medical contraindication for adjuvant endocrine treatment, if indicated
* Inability to absorb or understand the meaning of the study

Primary outcomes:
measure: iDFS
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
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