Clinical trial NCT04500262: Comparison Trial of Open-tip Pulsed Needle Biopsy and Conventional Core Biopsy in Axillary Lymph Nodes
Official title: Comparison Trial of Open-tip Pulsed Needle Biopsy and Conventional Core Biopsy in Axillary Lymph Nodes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Keywords: Breast Cancer
Axillary Lymph Nodes
Biopsy
Lead sponsor: NeoDynamics AB
Sponsor class: INDUSTRY
First posted: 2020-08-05
Enrollment: 479
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The aim of the study is to compare performance and safety of a newly developed 14-gauge open-tip pulsed biopsy needle with a conventional 14-gauge core biopsy needle for sampling of radiologically indeterminate or suspicious axillary lymph nodes in women with radiologically suspected breast cancer.

This is a Sponsor-initiated multicentre randomised trial. At the time of radiological breast cancer diagnosis women with ultrasonically abnormal lymph nodes undergo axillary sampling using the NeoNavia biopsy system or a common CNB device. This is in accordance with clinical routine and current clinical guidelines. The NeoNavia biopsy system is approved for use in the axillary lymph nodes.

Detailed description: It is the standard of care in the United Kingdom for women with suspected or confirmed breast cancer to undergo ultrasound of the ipsilateral axilla prior to surgery in order to detect nodal metastatic disease. Women with invasive breast cancer and normal axillary ultrasound will then undergo operative sentinel lymph node biopsy. This is usually at the same time as the surgical removal of the breast cancer by wide local excision or mastectomy but may be done as a separate procedure before (e.g. where neoadjuvant chemotherapy is planned) or after (e.g. if a non-operative diagnosis of invasive breast cancer was not made prior to surgery). Women who are found to have a positive sentinel lymph node biopsy (i.e. have axillary metastatic disease) normally undergo axillary node clearance (ANC) at a subsequent operation. This policy may change in the future, as evidence from the American Z0011 study suggests that women with low volume axillary metastatic disease do as well with no further axillary surgery plus standard adjuvant treatment as those that undergo ANC.

Women who have abnormal lymph nodes on axillary ultrasound undergo tissue sampling with core needle biopsy (CNB), usually 14 Gauge (14G) under local anaesthetic or with fine needle aspiration cytology (FNAC). Women with proven axillary nodal metastases will then usually undergo axillary node clearance at the same operation as surgical removal of the primary tumour.

The number of women who need to undergo more than one operation can therefore be minimised by maximising the number of women with axillary metastatic disease in whom this diagnosis is made preoperatively.

Meta-analyses of published studies and more recent studies suggest that ultrasound has a sensitivity of \~60% and specificity of \~80% for the detection of metastatic lymph nodes. Although no randomised comparisons of 14G core needle biopsy (CNB) and FNAC have been performed, several studies have suggested that CNB is more accurate. Ultrasound-guided biopsy of nodes subsequently proven at surgery to contain metastases has a sensitivity of \~80% and a specificity of 100% and is more likely to be positive in those women with a higher nodal burden. Numerous studies suggest that increasing the volume of tissue removed may increase the diagnostic yield.

Recently a new biopsy device indicated for the use in breast and axillary lymph nodes (NeoNavia biopsy system, NeoDynamics, Sweden) has become available. It incorporates a pneumatic needle insertion mechanism that is intended to provide better control of needle progression and enable stepwise insertion without noticeable deformation or displacement of surrounding tissue as visualized under ultrasound. Furthermore a new method of tissue acquisition is employed that has pre-clinically shown a significantly higher sampling yield compared to CNB. These characteristics indicate that the device could be well suited for axillary lymph node biopsies. Initial clinical results indicate that in axillary lesions deemed "technically difficult", i.e. where prior US-guided biopsies with CNB or FNA had yielded non-diagnostic histology results, the NeoNavia device performed successfully, thereby significantly altering clinical management.

Eligibility criteria: Inclusion Criteria:

* Women in screening and symptomatic clinics aged 18 years or older with breast masses scored as 1 of the following:

  * M3, M4 or M5 (mammographically uncertain, suspicious or highly suspicious of malignancy)
  * MRI5 (highly suspicious of malignancy on MRI)
  * U3, U4 or U5 (ultrasonically uncertain, suspicious or highly suspicious of malignancy)
  * have histologically proven breast cancer
* who have ipsilateral axillary lymph nodes which are described as indeterminate or suspicious for metastatic disease and indicated for biopsy, as determined by individual breast unit criteria
* are able to give informed consent for the study

Exclusion Criteria:

* Previous ipsilateral axillary surgery
* Target lymph node not suitable for needle biopsy due to its close proximity to critical structures such as major blood vessels
* Unable to give written informed consent in English

Primary outcomes:
measure: Comparison of adequacy rate of tissue sampling of axillary lymph nodes under local anaesthetic with open-tip pulsed needle biopsy (OT-PNB) and conventional 14-gauge core needle core biopsy (CNB)
timeFrame: After histopathological analysis of tissue samples, up to 1 week after biopsy
Secondary outcomes:
measure: Comparison of pain scores for the two biopsy techniques immediately post-procedure and the maximum from days 1-3 post-procedure
timeFrame: 1-14 days
measure: Comparison of complication rates between the two techniques
timeFrame: 0-14 days post-biopsy
measure: Comparison of the willingness of patients to undergo the procedure again if necessary
timeFrame: 4-14 days post-biopsy
measure: Comparison of number of tissue samples taken with the two techniques and the number of device insertions per subject
timeFrame: 1 day
measure: Comparison of the time taken for the two techniques (first biopsy device entry to last withdrawal)
timeFrame: 1 day
measure: Comparison of the total weight of tissue obtained with the two techniques and the average weight per device insertion
timeFrame: 1 day
measure: Users views upon whether the pulse technology of the NeoNavia® device facilitates accurate needle passage through the tissues to an optimum sampling position
timeFrame: 1 day
measure: Users views upon whether the pulse technology of the NeoNavia® device facilitates stabilisation of the target and control of the needle position
timeFrame: 1 day
measure: Comparison of sensitivity of preoperative axillary assessment of ultrasonically indeterminate or abnormal axillary lymph (calculated from the proportion of women with axillary metastatic disease at surgery).
timeFrame: post-surgery
measure: Comparison of intended outcome of biopsy procedure, i.e. number of samples to be taken from respective lymph node, and actual outcome
timeFrame: 1 day
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
city: Cheltenham
country: United Kingdom
facility: Thirlestaine Breast Centre, Gloucestershire Hospitals NHS Foundation
city: Darlington
country: United Kingdom
facility: Darlington Memorial Hospital
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
city: Edinburgh
country: United Kingdom
facility: Western General Hospital, Lothian NHS Trust
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust
city: Leeds
country: United Kingdom
facility: St James's University Hospital, Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: King Edward VII's Hospital, BARTS Health NHS Trust
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital, Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
city: Southend
country: United Kingdom
facility: Southend University Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden, The Royal Marsden NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Wycombe
country: United Kingdom
facility: High Wycombe Hospital
Study officials:
affiliation: Gloucestershire Hospitals NHS Foundation Trust
name: Sarah Vinnicombe, Dr
role: PRINCIPAL_INVESTIGATOR
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