E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast Cancer - Using SonoVue injected intradermally into the breast and contrast enhanced ultrasound to see if the cancer has spread via lymphatic channels to sentinel lymph nodes in the axilla. |
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E.1.1.1 | Medical condition in easily understood language |
Breast Cancer - Using SonoVue injected into the breast and contrast enhanced ultrasound to see if the cancer has spread through tissue fluid channels to the key sentinel lymph nodes in the armpit. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Hypothesis: In breast cancer patients with a normal conventional grey-scale axillary ultrasound, enhanced pre-operative axillary staging using intradermal microbubbles and contrast enhanced ultrasound (CEUS) is technically feasible for imaging specialists in the breast clinic. Visualising the lymphatic (tissue fluid) drainage of the breast with CEUS to identify and biopsy sentinel lymph nodes increases the sensitivity of ultrasound as a test to identify lymph node metastases.
Specific aims: 1. Is it technically feasible? - To determine whether imaging specialists in the UK after training and mentorship can reliably perform the technique of intradermally injected microbubbles and CEUS to successfully identify, core biopsy and clip mark armpit sentinel lymph nodes in patients with breast cancer. 2. Is it accurate?- To determine the overall diagnostic accuracy of a CEUS guided core biopsy as a test to identify sentinel lymph node metastases as compared to the current standard of armpit s |
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E.2.2 | Secondary objectives of the trial |
Other important outcomes will be: Is the procedure quick to perform? Compared to armpit surgery, does the core biopsy of sentinel lymph nodes cause more or less bleeding that needs an intervention? Compared to armpit surgery, does a core biopsy of sentinel lymph nodes cause more or less wound infections? Compared to armpit surgery, does a core biopsy of sentinel lymph nodes cause more of less pain and sensory disturbance? Compared to armpit surgery, are patients more or less satisfied with a core biopsy of sentinel lymph nodes using contrast enhanced ultrasound? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically confirmed invasive carcinoma of the breast without palpable axillary lymph nodes with planned primary surgical treatment. Normal B-mode axillary ultrasound or benign biopsy of morphologically abnormal lymph nodes. Participant is willing and able to give informed consent for participation in the trial. Aged 18 years or above. |
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E.4 | Principal exclusion criteria |
Previous ipsilateral breast cancer treated with radiotherapy or chemotherapy or recurrent breast cancer. Female participant who is pregnant, lactating or planning fertility preservation during the course of the trial. Allergy to contrast. Inflammatory or locally advanced breast cancer. Metastatic breast cancer. Inability to raise ipsilateral arm above head. Multiple medical co-morbidities (ASA 4 or above). Previous ipsilateral axillary surgery. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Technical feasibility will be assessed by 75% of imaging specialists achieving; >85% visualisation of tumour draining axillary sentinel nodes, >80% successful core biopsy (lymph node tissue retrieved) rate and >80% concordance with sentinel nodes identified surgically with radio-isotope and blue dye. Diagnostic performance will be assessed by calculating the overall pooled sensitivity, specificity, positive predictive value, negative predictive value of intradermally injected SonoVue and contrast enhanced ultrasound guided core biopsy as a test to identify sentinel node metastases as compared to axillary surgery and the prevalence of lymph node metastases. An overall sensitivity >50% will be considered acceptable. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The trial will run for 18 months. |
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E.5.2 | Secondary end point(s) |
To establish the whole time taken to intradermally inject SonoVue and follow the contrast into the axilla and perform a core biopsy of sentinel lymph nodes. To assess the volume of metastatic axillary disease (number of lymph nodes with metastases) at the end of primary surgical treatment. To determine the level of complications (bleeding, infections and pain/sensory disturbances) of the procedure compared to axillary surgery. To assess patient satisfaction with the procedure compared to armpit surgery. To conduct a prospective audit of each unit’s detection rate of lymph node metastases with conventional B-mode axillary ultrasound.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The trial will run for 18 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |