Individualized Locoregional Treatment of Initially Biopsy-proven Node-positive Breast Cancer After Primary Systemic Therapy

NCT04281355 | Withdrawn Phase 3 DMC

• 1 other identifier: EUBREAST-2 INDAX
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• iDFS

  Invasive disease-free survival

  5 years

Study Arms (2)

Randomisation A - Intervention

EXPERIMENTAL

In pathologically node-negative patients on axillary staging (TAD, TLNB, SLNB) after primary systemic treatment, no regional radiotherapy is given and no axillary lymph node dissection are performed.

Procedure: Omission of axillary lymph node dissection; Radiation: Omission of regional irradiation

Randomisation B - Intervention

EXPERIMENTAL

In pathologically node-positive patients on axillary staging (TAD, TLNB, SLNB) after primary systemic treatment, full axillary and regional radiotherapy is given but no axillary lymph node dissection performed.

Procedure: Omission of axillary lymph node dissection

Interventions

Omission of axillary lymph node dissection PROCEDURE

Axillary lymph node dissection will be replaced by axillary radiotherapy in Randomisation B

Randomisation A - Intervention; Randomisation B - Intervention

Omission of regional irradiation RADIATION

Regional irradiation will be omitted in the interventional arm of Randomisation A.

Randomisation A - Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: February 24, 2020
• Study Start: January 1, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 25, 2021

Record last verified: 2021-02