Comparing surgical treatments for people with early breast cancer that has spread to the armpit (axillary) lymph nodes: targeted armpit surgery (targeted axillary dissection) versus standard armpit surgery (axillary node clearance)
| ISRCTN | ISRCTN71954670 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71954670 |
| IRAS number | 333212 |
| ClinicalTrials.gov number | Nil Known |
| Secondary identifying numbers | CPMS 58409, NIHR158400 |
- Submission date
- 06/06/2025
- Registration date
- 18/07/2025
- Last edited
- 18/07/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Breast cancer affects 55,000 patients each year in the UK, and in ~20% of cases, the cancer will have spread to the armpit (axillary) lymph nodes. The current standard treatment for these patients is to remove all the axillary lymph nodes (axillary node clearance), even if only one or two are affected. However, one in three patients will experience life-changing complications as a result of this treatment, including permanent swelling of the arm (lymphoedema), long-term pain, and problems with shoulder function. These complications dramatically affect quality of life and are costly to the NHS. Axillary node clearance (ANC) was believed to give patients the best chance of surviving their breast cancer, but there is no evidence to show that this is true if the spread to the axillary lymph nodes is limited. More targeted surgery to the armpit, called a targeted axillary dissection (TAD), in which just the lymph nodes containing cancer and the first draining (sentinel) lymph nodes are removed, may be just as safe and reduce the risk of life-changing complications. The TADPOLE study aims to determine whether targeted armpit surgery (TAD) reduces the risk of lymphoedema at 12 months after the operation without increasing the risk of the cancer returning, compared to ANC.
Who can participate?
Adults diagnosed with primary T1-2 breast cancer, with limited spread of the cancer to their armpit lymph nodes ( i.e. 2 or fewer lymph nodes affected) being treated at any hospital participating in the TADPOLE study. Detailed clinical inclusion and exclusion criteria apply and will be assessed by a clinician/surgeon at the participating hospital.
What does the study involve?
Participants will undertake clinical assessments at baseline, including measurements of arm circumference, and will be asked to complete health-related quality of life questionnaires. All participants will be followed up in person during a hospital visit for the 1-year follow-up. All other follow-ups will be done remotely by telephone at 1 month and then 2, 3, 4 and 5 years after surgery for a range of clinical, safety, and patient-reported outcomes. Participants are required to complete health-related quality of life questionnaires at 1, 2 and 5 years. Mammograms will also be performed yearly for 5 years, as per standard care. Participants will be randomised at a 2:1 ratio to TAD:ANC. Participants may also take part in an interview to discuss their experiences of the study if they wish to.
What are the possible benefits and risks of participating?
Please see the TADPOLE supplementary Participant Information Leaflet, available on the TADPOLE study website, for further information about the risks and benefits of participating
Where is the study run from?
The Bristol Trials Centre, a UK Clinical Research Collaboration registered Clinical Trials Unit, which is part of the University of Bristol’s Medical School, is running the study
When is the study starting and how long is it expected to run for?
September 2023 to July 2033. Recruitment to the study is expected to start in September 2025 and will continue for 28 months. Following this, there will be 5 years of follow-up, so the study results will not be expected until 2033.
Who is funding the study?
The National Institute of Health and Social Care Research (NIHR) – Health Technology Assessment Programme (NIHR-HTA)
Who is the main contact?
Study coordinator (Lucy Dabner) Tadpole-trial@bristol.ac.uk
Cancer Research UK plain English summary link added to plain English summary field
Contact information
Public
Bristol Trials Centre, Bristol Medical School, University of Bristol, 1-5 Whiteladies Road, Clifton
Bristol
BS8 1NU
United Kingdom
| Phone | +44 0117 45 51524 |
|---|---|
| Tadpole-trial@bristol.ac.uk |
Scientific, Principal Investigator
University of Bristol, Level 2, Learning and Research building
Bristol
BS10 5NB
United Kingdom
| shelley.potter@bristol.ac.uk |
Study information
| Study design | Multi-centre parallel-group pragmatic phase III randomized controlled trial with a 9-month internal pilot phase and embedded qualitative research plus quality assurance and health economic analysis and Study Within A Trial (SWAT) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home, Hospital, Telephone |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Targeted axillary dissection versus axillary node clearance in patients with positive axillary lymph nodes in early breast cancer: a multicentre, pragmatic, phase III randomised controlled trial |
| Study acronym | TADPOLE v1.0 |
| Study objectives | The hypothesis is that targeted armpit surgery (targeted axillary dissection) reduces the risk of lymphoedema at 12 months after the operation without increasing the risk of the cancer returning, compared to standard armpit surgery (axillary node clearance). |
| Ethics approval(s) |
Submitted 23/04/2025, Wales Research Ethics Committee 3 (Health and Care Research Wales, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 02922 941107; Wales.REC3@wales.nhs.uk), ref: 25/WA/0139 |
| Health condition(s) or problem(s) studied | Adults diagnosed with primary T1-2 breast cancer, with low nodal disease |
| Intervention | The TADPOLE trial is a multi-centre, parallel group, pragmatic phase 3 randomised controlled trial with a 9-month internal pilot phase, embedded qualitative research, surgical and radiotherapy quality assurance (QA), health economic analysis and Study Within A Trial (SWAT). Patients with early breast cancer and low volume nodal disease (i.e. the cancer has spread to 2 or fewer lymph nodes) undergoing surgery as their first treatment will be randomised in a 2:1 ratio to receive either targeted axillary dissection (TAD) or axillary node clearance (ANC), respectively. The internal pilot will establish whether sufficient numbers of eligible patients can be identified, recruited and will adhere to their allocated treatment for the trial to robustly answer the trial questions. The internal pilot will last for 9 months. If the progression criteria are met, the main trial recruitment will continue for a further 19 months (total recruitment 28 months) at a minimum of 40 UK sites. If the main trial proceeds, patients from the internal pilot will be included in the final analysis. All participants will be followed up for 5 years post-surgery. Consent will be obtained for long-term (10-and 20-year) follow-up via linkage to routinely collected data, subject to funding. Patients with breast cancer and low-volume nodal disease recommended for primary surgery by the local site's Multi-Disciplinary Team (MDT) meeting will be screened. Potentially eligible participants will be provided with information about the trial using a layered approach. They will initially be informed about the study at a clinic appointment with their surgeon, at which their breast cancer diagnosis and the initial treatment plan are discussed. This appointment will include a description of both the TAD and ANC procedures and the risks and benefits of both options. Patients will be supported by their clinical nurse specialist (breast care nurse) and will be allowed to ask questions. Clinical/research teams at participating sites will then follow up with the patient to answer any questions. If the patient would like to participate, they will arrange a baseline visit, which will be timed to coincide with another hospital appointment (if possible). Once written informed consent has been provided, patients will be randomised by computer during (or shortly after) their baseline visit to receive either TAD or ANC alongside their primary breast surgery. Randomisation will take place before surgery to allow enough time for theatre list planning (TAD is a shorter procedure than ANC); patients to be effectively counselled about their allocated procedure, and for participants allocated to TAD to have an additional ultrasound procedure to mark the involved lymph node(s). Patients will undertake clinical assessments at baseline, including measurements of their arm circumference, and will be asked to complete health-related quality of life questionnaires. All participants will be followed up in person during a hospital visit for the 1-year follow-up. All other follow-ups will be done remotely by telephone at 1 month and then 2, 3, 4 and 5 years after surgery for a range of clinical, safety and patient-reported outcomes. Participants can also choose to have all their follow-ups in person if they prefer, and the local site has capacity. Participants will be required to complete health-related quality of life questionnaires at 1, 2 and 5 years. Mammograms will also be performed yearly for 5 years, as per standard care. Some patients will also be invited to take part in the embedded qualitative study and can optionally consent to the trial team audio-recording the interviews about their experience. Some patients who decline to participate in the study will also be approached to take part in qualitative interviews about their reasons for not taking part. A Study Within A Trial is also embedded into TADPOLE, where an evaluation of language and interpretation services used in TADPOLE will take place to assess how these have facilitated the recruitment of low-level English-speaking participants from ethnic minority groups. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | The following co-primary outcome measures will be assessed: 1. Lymphoedema at 12 months post-surgery, defined as BOTH an objective increase in arm circumference of >2cm from baseline, and using two items from the validated Lymphoedema and Breast Cancer Questionnaire (LBCQ) for patients to self-report lymphoedema symptoms defined as a response of ‘yes’ to both: arm “swelling now” and arm “heaviness in the past year” from. A composite endpoint combining objective and patient-reported outcomes was considered important to minimise potential bias in the trial. 2. Locoregional recurrence (LRR) at 5 years, defined as pathologically and/or radiologically confirmed recurrent tumour in the ipsilateral breast after breast conserving surgery or the skin or soft tissues of the chest wall within the anatomical boundaries of the breast after mastectomy; ipsilateral axilla, infraclavicular, supraclavicular fossa, interpectoral area or ipsilateral internal mammary chain. The date of locoregional recurrence will be the date on the imaging or pathology report, whichever comes first. |
| Secondary outcome measures | The following secondary outcome measures will be collected (all timepoints are measured from post-last axillary surgery): 1. Surgical complications measured using data collected from the electronic case report form (eCRF) at 1-month post-surgery 2. Surgical and oncological outcomes measured using data collected from patient medical records at 1-month post-surgery 3. Patient-reported lymphoedema assessed using two questions from the LBCQ questionnaire (as per primary outcome) at 12, 24 and 60 months 4. Objective assessment of lymphoedema using measurement of arm circumference at 12 months 5. Arm and shoulder morbidity measured using the QuickDASH questionnaire at 12, 24 and 60 months 6. Pain measured using the Numerical Pain Rating Scale (NPRS) at 1 and 12 months 7. Overall and disease-free survival measured using data collected from patient medical records at 60 months 8. Health-related quality of life measured using the EQ-5D-5L, FACT-B+4 and LYMPH-Q at 12, 24, and 60 months 9. Resource use to estimate costs measured using the ModRUM questionnaire and data collected from the patient’s medical records at 12, 24, 60 months and modelled beyond the end of the trial |
| Overall study start date | 04/09/2024 |
| Completion date | 31/07/2033 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 861; UK Sample Size: 861 |
| Key inclusion criteria | ALL of the following must apply: 1. Adults (> = 18 years of age) 2. Primary T1-2 breast cancer of any grade (multifocal/multicentric disease is permitted) 3. Low volume N1 axillary nodal disease confirmed on core biopsy or fine needle aspiration cytology, defined as: 3.1. Clinically normal (cN0) 3.2. Radiologically detected nodal involvement 3.3. With < = 2 involved nodes on USS 4. Able and willing to provide written informed consent 5. Willing, fit and able to undergo primary surgical treatment |
| Key exclusion criteria | Participants may not enter the study if ANY of the following apply: 1. > = 3 suspicious nodes on USS or clinically abnormal nodes (cN1) 2. T3 or T4 disease by clinical or radiological assessment 3. Pure invasive lobular carcinoma 4. Bilateral breast cancer 5. Previous ipsilateral breast cancer or ductal carcinoma in situ 6. Received neoadjuvant systemic anticancer therapy (neoSACT) 7. Received neoadjuvant endocrine therapy (defined as > 4 weeks of treatment) 8. Previous axillary surgery (sentinel node biopsy, axillary node clearance or axillary sample) 9. Other invasive cancers unless: 9.1. Disease-free for 5 years or 9.2. Previous basal cell carcinoma, cervical carcinoma in situ, non-muscle invasive urothelial carcinoma 10. High-risk group for developing breast cancer as defined by NICE guidance 11. Pregnant or breastfeeding 12. Any serious and/or unstable pre-existing medical, psychiatric or other condition that would prevent compliance with the trial or consent process 13. Prisoners |
| Date of first enrolment | 01/09/2025 |
| Date of final enrolment | 31/12/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Hospital/treatment centre
Research & Development, Learning & Research (Level 3), Southmead Hospital, Southmead Road, Westbury-On-Trym
Bristol
BS10 5NB
England
United Kingdom
| Phone | +44 0117 414 9330 |
|---|---|
| researchsponsor@nbt.nhs.uk | |
| Website | https://www.nbt.nhs.uk/ |
"ROR" |
https://ror.org/036x6gt55 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/07/2033 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Available on request |
| Publication and dissemination plan | The study findings/results will be disseminated by usual academic channels, i.e. presentation at international meetings, as well as by peer-reviewed publications and through patient organisations and newsletters to patients, where available. This will include consideration of sharing findings with patients and the public from different community groups and the use of social media to engage the wider population. Where possible, information will be disseminated to participating sites and participants in line with timelines for academic audiences (i.e. participants and sites being informed of the study results on or shortly after the date the academic paper is published). Before dissemination materials are drafted, PPI members will be consulted on the proposed methods for dissemination to non-academic audiences. The first co-primary outcome results paper (regarding lymphoedema) will be published approximately 18 months after recruitment finishes. The 2nd co-primary outcome results paper (locoregional recurrence) will be published in 2033. Other publications relating to TADPOLE will be published as agreed by the Trial Management Group. |
| IPD sharing plan | After the study ends, the data will be deposited at the University of Bristol Research Data Repository (data.bris.ac.uk/data), where, once published, they will be assigned a DOI. A metadata record will be published openly by the repository, and this record will clearly state how data can be accessed by bona fide researchers. Access requests will be directed to the Research Data team at the University of Bristol, who will assess the motives of potential data re-users before granting access to the data. Only anonymised data will be shared, and only participants who consented to this will be included in the dataset. |
Editorial Notes
06/06/2025: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
