ATNEC: Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy

Sponsor
University Hospitals of Derby and Burton NHS Foundation Trust (Other)
Overall Status
Recruiting
CT.gov ID
NCT04109079
Collaborator
(none)
1,900
56
2
108.1
33.9
0.3

Study Details

Study Description

Brief Summary

The aim of this study is to assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Axillary lymph node dissection
  • Radiation: Axillary radiotherapy
  • Radiation: Breast or chest wall radiotherapy
N/A

Detailed Description

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease.

Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.

Methods:

Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio.

Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node).

Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years.

Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years.

Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness.

Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years.

Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated.

Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1900 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
ATNEC - Axillary Management in T1-3N1M0 Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases at Presentation After Neoadjuvant Chemotherapy
Actual Study Start Date :
Feb 26, 2021
Anticipated Primary Completion Date :
Feb 28, 2030
Anticipated Study Completion Date :
Feb 28, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: No axillary treatment

Patients in this arm will not receive axillary treatment (axillary lymph node dissection or axillary radiotherapy). Supraclavicular fossa radiotherapy is not allowed when randomised to this arm.

Radiation: Breast or chest wall radiotherapy
Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

Active Comparator: Axillary treatment

Patients in this arm will receive axillary treatment. Axillary treatment can be axillary lymph node dissection or axillary radiotherapy.

Procedure: Axillary lymph node dissection
Participants will undergo removal of at least level I and II axillary lymph nodes.

Radiation: Axillary radiotherapy
Axillary radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

Radiation: Breast or chest wall radiotherapy
Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

Outcome Measures

Primary Outcome Measures

  1. Disease free survival (DFS) [5 years]

    DFS calculated as the time from randomisation until the date of first event of either a loco-regional invasive breast cancer relapse, distant relapse, ipsilateral or contralateral new invasive primary breast cancer or death by any cause or the censor date.

  2. Patient reported lymphoedema [5 years]

    Lymphoedema is self-reported based on two items from the validated Lymphoedema and Breast Cancer Questionnaire (arm "swelling now" and arm "heaviness in the past year"). Lymphoedema is defined as 'yes' to both questions.

Secondary Outcome Measures

  1. Arm function [5 years]

    Arm function will be assessed using shortened version of the Disability of the Arm, Shoulder and Hand (DASH), the 11-item QuickDASH questionnaire. Physical disability is defined as a change from baseline in the QuickDASH score of at least 14 points.

  2. Health related quality of life: EQ-5D-5L [5 years]

    Health related quality of life will be assessed with EQ-5D-5L

  3. Axillary recurrence free interval [5 years]

    Axillary recurrence free interval, calculated from the date of randomisation to the date of axillary recurrence or the censor date.

  4. Overall survival [5 years]

    Overall survival calculated as the time from randomisation until the date of death by any cause or the censor date.

  5. Local (breast or chest wall) recurrence [5 years]

    Number of participants with local (breast or chest wall) recurrence

  6. Regional (nodal) recurrence [5 years]

    Number of participants with regional (nodal) recurrence

  7. Distant metastasis [5 years]

    Number of participants with distant metastasis.

  8. Contralateral breast cancer [5 years]

    Number of participants with contralateral breast cancer.

  9. Non-breast cancer [5 years]

    Number of participants with non-breast cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • T1-3N1M0 breast cancer at diagnosis (prior to NACT) by American Joint Committee on Cancer (AJCC) staging 7th edition

  • Fine-needle aspiration (FNA) or core biopsy confirmed axillary nodal metastases at presentation

  • Oestrogen receptor, progesterone receptor and HER2 status evaluated on primary tumour

  • Received standard NACT as per local guidelines

  • Ultrasound of the axilla at completion of NACT

  • Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node). If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least 3 nodes removed (including the marked node).

  • No nodal metastases post NACT (isolated tumour cells, micro or macrometastasis)

Exclusion Criteria:
  • Bilateral invasive breast cancer

  • Sentinel node biopsy prior to NACT

  • Marked node not removed except where the node/s removed show

  • evidence of downstaging with complete pathological response e.g. fibrosis or scarring

  • Previous axillary surgery on the same body side as the scheduled targeted sampling

  • Radiation therapy for the currently diagnosed breast cancer prior to randomisation

  • Previous cancer within 5 years or concomitant malignancy except

  • basal or squamous cell carcinoma of the skin

  • in situ carcinoma of the cervix

  • in situ melanoma

  • contra- or ipsilateral in situ breast cancer

Contacts and Locations

Locations

Site City State Country Postal Code
1 Airedale NHS Foundation Trust Keighley Bd20 6td United Kingdom
2 North Cumbria Integrated Care NHS Foundation Trust Carlisle Ca2 7hy United Kingdom
3 Frimley Health NHS Foundation Trust Camberley Gu16 7uj United Kingdom
4 NHS Highland Inverness Iv2 3uj United Kingdom
5 James Paget University Hospitals NHS Foundation Trust Great Yarmouth Nr31 6la United Kingdom
6 Royal Berkshire NHS Foundation Trust Reading Rg1 5an United Kingdom
7 East Cheshire NHS Trust Macclesfield Sk10 3bl. United Kingdom
8 The Shrewsbury and Telford Hospitals NHS Trust Shrewsbury Sy3 8xq United Kingdom
9 NHS Grampian Aberdeen United Kingdom AB25 2ZN
10 Sandwell and West Birmingham NHS Trust Birmingham United Kingdom B18 7QH
11 Bolton NHS Foundation Trust Bolton United Kingdom BL4 0JR
12 Bradford Teaching Hospitals NHS Foundation Trust Bradford United Kingdom BD5 0NA
13 Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom CB2 0QQ
14 Countess of Chester Hospital NHS Trust Chester United Kingdom CH2 1HJ
15 Mid Cheshire NHS Foundation Trust Crewe United Kingdom CW1 4QJ
16 County Durham and Darlington NHS Foundation Trust Darlington United Kingdom DL3 6HX
17 University Hospitals of Derby and Burton NHS Foundation Trust Derby United Kingdom DE22 3NE
18 NHS Dumfries and Galloway Dumfries United Kingdom DG2 8RX
19 NHS Fife Dunfermline United Kingdom KY12 0SU
20 NHS Lanarkshire East Kilbride United Kingdom G75 8RG
21 NHS Lothian Edinburgh United Kingdom EH4 2XU
22 Royal Devon and Exeter NHS Foundation Trust Exeter United Kingdom EX2 5DW
23 Gateshead Health NHS Foundation Trust Gateshead United Kingdom NE9 6SX
24 Wye Valley NHS Trust Hereford United Kingdom HR1 2ER
25 Calderdale and Huddersfield NHS Foundation Trust Huddersfield United Kingdom HD3 3EA
26 Hull University Teaching Hospitals NHS Trust Hull United Kingdom HU16 5JQ
27 NHS Forth Valley Larbert United Kingdom FK5 4WR
28 Leeds Teaching Hospitals NHS Trust Leeds United Kingdom LS9 7TF
29 University Hospitals of Leicester NHS Trust Leicester United Kingdom LE3 9QP
30 Hywel Dda University Health Board Llanelli United Kingdom SA14 8QF
31 North Middlesex University Hospital NHS Trust London United Kingdom N18 1QX
32 University College London Hospitals NHS Foundation Trust London United Kingdom NW1 2BU
33 Royal Free London NHS Foundation Trust London United Kingdom NW3 2QG
34 King's College Hospital NHS Foundation Trust London United Kingdom SE5 9RS
35 The Royal Marsden NHS Foundation Trust London United Kingdom SM2 5PT
36 Imperial College Healthcare NHS Trust London United Kingdom W6 8RF
37 Bedfordshire Hospitals NHS Foundation Trust Luton United Kingdom LU4 0DZ
38 Manchester University NHS Foundation Trust Manchester United Kingdom M8 5RB
39 NHS Borders Melrose United Kingdom TD6 9BS
40 South Tees Hospitals NHS Foundation Trust Middlesbrough United Kingdom TS4 3BW
41 Milton Keynes University Hospital NHS Trust Milton Keynes United Kingdom MK6 5LD
42 Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle Upon Tyne United Kingdom NE1 4LP
43 Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom OX3 7LE
44 St Helens and Knowsley Teaching Hospitals NHS Trust Prescot United Kingdom L35 5DR
45 The Rotherham NHS Foundation Trust Rotherham United Kingdom S60 2UD
46 West Hertfordshire Hospitals NHS Trust St Albans United Kingdom AL3 5PN
47 North Tees and Hartlepool NHS Foundation Trust Stockton-on-Tees United Kingdom TS19 8PE
48 University Hospitals of North Midlands NHS Trust Stoke-on-Trent United Kingdom ST4 6QG
49 Somerset NHS Foundation Trust Taunton United Kingdom TA1 5DA
50 Royal Cornwall Hospitals NHS Trust Truro United Kingdom TR1 3LJ
51 Mid Yorkshire Hospitals NHS Trust Wakefield United Kingdom WF1 4DG
52 Mid and South Essex NHS Foundation Trust Westcliff-on-Sea United Kingdom SS0 0RY
53 Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust Wigan United Kingdom WN1 2NN
54 Clatterbridge Cancer Centre NHS Foundation Trust Wirral United Kingdom CH63 4JY
55 Wirral University Teaching Hospital NHS Foundation Trust Wirral United Kingdom CH63 4JY
56 Yeovil District Hospital NHS Trust Yeovil United Kingdom BA21 4AT

Sponsors and Collaborators

  • University Hospitals of Derby and Burton NHS Foundation Trust

Investigators

  • Principal Investigator: Amit Goyal, MS, MD, FRCS, Royal Derby Hospital, Derby, UK

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Dr Amit Goyal, Consultant Oncoplastic Breast Surgeon & Associate Professor, University Hospitals of Derby and Burton NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT04109079
Other Study ID Numbers:
  • NIHR 128311
First Posted:
Sep 30, 2019
Last Update Posted:
Aug 9, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Dr Amit Goyal, Consultant Oncoplastic Breast Surgeon & Associate Professor, University Hospitals of Derby and Burton NHS Foundation Trust
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 9, 2022