Clinical trial NCT04468113: Clip Marker Placement in Primary Lesions of Breast Cancer Patients Receiving Neoadjuvant Therapy
Official title: Prospective, Multicenter Registry Study Evaluating the Feasibility of Ultrasound-guided Clipping of Suspicious Intramammary Lesions in Primary Breast Cancer Patients Receiving Neoadjuvant Therapy (Ultra3Detect)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Primary Breast Cancer
Keywords: breast cancer
clip
ultrasound
neoadjuvant therapy
Lead sponsor: Kliniken Essen-Mitte
Sponsor class: OTHER
First posted: 2020-07-13
Enrollment: 339
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Female patients with sonographically suspicious unilateral or bilateral intramammary foci, scheduled for sonography-guided core biopsy and marking of the lesion with the Tumark® Vision Clip.

Brief summary: Neoadjuvant systemic therapy (NST) is increasingly recommended for patients with early breast cancer, and the rate of patients with pathological complete remission (pCR) is increasing due to the use of modern chemotherapy regimens and targeted therapies, especially in patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer and triple negative breast cancer (TNBC). It is therefore important to mark a lesion (with e.g. clip) before the start of NST in order to safely identify and localize a clip and (former) tumor bed after completion of NST. Reliable sonographic detection of the clip would be preferred to mammography-guided detection and marking. In addition to avoiding radiation exposure by mammography and reducing time, personnel and financial expenditure, ultrasound-guided wire marking of the clip is less painful for the patient than stereotactic wire marking.

The present prospective registry study aims to evaluate how often the intramammary Tumark® Vision clip can be detected by ultrasound after completion of NST in patients with TNBC and HER2+ breast cancer and thus, in the case of pCR, how often the elaborate clipping with mammographic (stereotactic) guidance can be avoided.

Detailed description: Breast cancer patients whose carcinomas have an aggressive tumor biology which implies the need for chemotherapy are increasingly being treated with NST. As a standard procedure, clip placement of the suspicious lesion is performed after ultrasound-guided core biopsy or mammography-guided vacuum biopsy. Clipping is necessary to enable the clear identification of the sonographically suspicious area of the breast and safe surgical removal of the remaining tumor tissue (if any) during a later surgery, even following a good response under NST. The placement of a marker (clip) is particularly important for the precise localization of the original tumor bed in patients with pCR.

There are a number of commercially available markers (clips) which are indicated for intramammary marking of a lesion and which differ in terms of shape and material. Difficulties may arise in placing the clip in the tumor or the tumor center. In addition, the clip can dislocate from the initial location and/or the clip might not be visualized during response monitoring. Evaluations of the ultrasound-visible clip made of nitinol investigated in this study showed very good results regarding marker dislocation and visibility within 7 days after inital placement.The clip, which immediately unfolds into a 3-dimensional spherical structure after insertion into the tissue, could be detected by both sonography and mammography in all 50 cases after the intervention; however, long-term data data at follow-up controls during and after NST are not available so far.

According to current German guidelines, imaging-assisted wire marking is recommended without restriction before breast conserving surgery for non-palpable lesions. The clip is considered the target lesion for wire marking, which can be done under sonographic or stereotactic control. If the clip is reliably visible on ultrasound (even in patients with pCR), the stereotactic control of wire marking can be omitted. Therefore, the ability to visualize a clip in breast ultrasonography is of great importance.

The present multicenter study aims to evaluate the sonographic detection rate of the intramammary Tumark® Vision clips after NST in clinical routine and the proportion of cases in which the clip cannot be detected, and thus the rate of mammography-guided wire markings.

Eligibility criteria: Inclusion Criteria:

* female patient aged ≥ 18 years
* written informed consent
* patient's consent to NST
* suspicious unilateral or bilateral intramammary foci that can be safely identified by ultrasound
* no evidence of distant metastasis (complete staging does not have to be present at inclusion)
* indication for breast conserving therapy
* no prior clip placement in the confirmed intramammary carcinoma
* patient is able to undergo NST treatment (even if the indication based on tumor biology is not yet available)
* high compliance and high number of planned relevant surgical interventions in participating study center
* patient can understand the scope of this prospective registry study

Exclusion Criteria:

* allergy to titanium and/or nickel
* pregnancy
* ipsilateral relapse (when NST: no exclusion criterion)
* prior extensive breast surgery (starting from quadrant resection)
* inflammatory breast cancer
* extramammary breast cancer
* multicentric or multifocal breast cancer
* patient is not operable
* patient is already undergoing adjuvant/neoadjuvant therapy
* inability to understand the purpose of the clinical trial or to comply with study procedures

Primary outcomes:
measure: Sonographic detection rate of clip at the time of surgery after completion of NST
timeFrame: At the time of surgery
Secondary outcomes:
measure: Number of ultrasound-guided clip placements per patient
timeFrame: Immediately after placement of clip
measure: Rate of successful clip placements in the tumor center
timeFrame: Immediately after placement of clip
measure: Visibility of the device (Tumark® Vision) cannula
timeFrame: During placement of clip
measure: Complications associated with the application of the clip
timeFrame: Up to 6 months after placement of clip
measure: Sonographic detection rate of clips in patients receiving NST
timeFrame: Immediately after placement of clip as well as after 4-8, 9-12, 13-26 weeks of NST treatment and preoperatively
measure: Sonographic detection rate of clips in TNBC and HER2+ patients receiving NST
timeFrame: Immediately after clip placement as well as after 4-8, 9-12, 13-26 weeks of NST treatment and preoperatively
measure: Sonographic detection rate of clips in all patients receiving NST and with pCR
timeFrame: Immediately after clip placement as well as after 4-8, 9-12,13-26 weeks of NST treatment and preoperatively
measure: Sonographic detection rate of clips in patients not receiving NST
timeFrame: Immediately after clip placement and preoperatively
measure: Intraoperative detection rate of the clip in specimen radiographs
timeFrame: At the time of surgery
measure: Intraoperative detection rate of the clip on specimen utrasound images
timeFrame: At the time of surgery
measure: Proportion of patients requiring preoperative, mammography-guided wire marking
timeFrame: Preoperatively
measure: Proportion of patients with mammographic verification after sonographic wire-marking
timeFrame: Preoperatively
measure: Proportion of patients with artifacts caused by clips
timeFrame: Up to 6 months after placement of clip
measure: Number of patients with complete pathological remission
timeFrame: Up to 10 weeks after surgery
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Interdisciplinary Breast Unit, Kliniken Essen-Mitte
Study officials:
affiliation: Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Germany
name: Sherko Kuemmel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Germany
name: Mattea Reinisch, MD
role: STUDY_CHAIR
affiliation: Department of Gynecology, Breast Center, Heidelberg University, Germany
name: Jörg Heil, MD, PhD
role: STUDY_CHAIR
References:
citation: Ruland AM, Hagemann F, Reinisch M, Holtschmidt J, Kummel A, Dittmer-Grabowski C, Stoblen F, Rotthaus H, Dreesmann V, Blohmer JU, Kummel S. Using a New Marker Clip System in Breast Cancer: Tumark Vision(R) Clip - Feasibility Testing in Everyday Clinical Practice. Breast Care (Basel). 2018 Apr;13(2):116-120. doi: 10.1159/000486388. Epub 2018 Mar 9.
citation: Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. doi: 10.1016/S1470-2045(17)30716-7. Epub 2017 Nov 23.
citation: von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.
citation: Shah AD, Mehta AK, Talati N, Brem R, Margolies LR. Breast tissue markers: Why? What's out there? How do I choose? Clin Imaging. 2018 Nov-Dec;52:123-136. doi: 10.1016/j.clinimag.2018.07.003. Epub 2018 Jul 6.