Comparison Trial of Open-tip Pulsed Needle Biopsy and Conventional Core Biopsy in Axillary Lymph Nodes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison Trial of Open-tip Pulsed Needle Biopsy and Conventional Core Biopsy in Axillary Lymph Nodes

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Open-tip pulsed needle biopsy (NeoNavia Biopsy System)
* Device: Core needle biopsy (CNB)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Open-tip pulsed needle biopsy<br>Biopsy procedure using the NeoNavia biopsy system. The needle used in this study is of the same outside diameter as a standard biopsy needle used in the breast or axilla (14-gauge) but does not have a notched trochar like a conventional spring-loaded device. It does not have a redundant portion of needle beyond the sampling zone and takes full circumference cylindrical cores. A pneumatic system powered by a floor-standing base unit connected via a handheld driver to the biopsy device provides impulses to the needle, allowing the operator to advance the needle through tissue with little manual force (NeoNavia biopsy system, NeoDynamics, Sweden). | Device: Open-tip pulsed needle biopsy (NeoNavia Biopsy System)<br>* Ultrasound-guided biopsy using 14G open-tip pulsed biopsy needle<br>|
| Active Comparator: Conventional core needle biopsy (CNB)<br>Standard of care core needle biopsy used currently in clinics for biopsy procedures | Device: Core needle biopsy (CNB)<br>* Ultrasound-guided biopsy using standard of care core needle biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | After histopathological analysis of tissue samples, up to 1 week after biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of pain scores for the two biopsy techniques immediately post-procedure and the maximum from days 1-3 post-procedure | Pain questionnaire administered to the participant immediately following the procedure and 4-14 days post procedure (relating to days 1-3 post procedure). Scale 0-10; 0 means no pain, 10 is the worst pain imaginable. | 1-14 days | 
| Comparison of complication rates between the two techniques | Collection of AE's, SAE's and device deficiencies | 0-14 days post-biopsy | 
| Comparison of the willingness of patients to undergo the procedure again if necessary | Questionnaire administered to the participant on clinic visit for biopsy result | 4-14 days post-biopsy | 
| Comparison of number of tissue samples taken with the two techniques and the number of device insertions per subject | Biopsy procedure data collected in real time | 1 day | 
| Comparison of the time taken for the two techniques (first biopsy device entry to last withdrawal) | Biopsy procedure data collected in real time | 1 day | 
| Comparison of the total weight of tissue obtained with the two techniques and the average weight per device insertion | Samples are weighed in clinic or pathology following the procedure | 1 day | 
| Users views upon whether the pulse technology of the NeoNavia® device facilitates accurate needle passage through the tissues to an optimum sampling position | Yes/No, questionnaire given to radiologist | 1 day | 
| Users views upon whether the pulse technology of the NeoNavia® device facilitates stabilisation of the target and control of the needle position | Yes/No, questionnaire given to radiologist | 1 day | 
| 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). | 14-200 days | post-surgery | 
| Comparison of intended outcome of biopsy procedure, i.e. number of samples to be taken from respective lymph node, and actual outcome | Biopsy procedure data | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Axillary Lymph Nodes, Biopsy