Intelligent Vacuum Assisted Biopsy Immediately Before Surgery As an Intra- or Pre-Operative Surrogate for Patient Response to Neoadjuvant Chemotherapy for Breast Cancer (VISION I)

Intelligent Vacuum Assisted Biopsy Immediately Before Surgery As an Intra- or Pre-Operative Surrogate for Patient Response to Neoadjuvant Chemotherapy for Breast Cancer (VISION I): a Multicenter Prospective Feasibility Trial

Neoadjuvant chemotherapy (NAC) is common practice in the primary treatment of breast cancer, leading to a complete pathologic remission (pCR) of the tumor in more than 50% in aggressive tumor types. As NAC induces different response patterns, radiologic imaging is not sufficiently accurate in predicting residual disease. Because of this uncertainty, surgery is so far the only valid option to either ascertain complete response or to remove the complete residual disease.

Vacuum-assisted biopsy (VAB) with the possibility of obtaining tissue of the former tumor center could contribute more reliably to detect any residual tumor or respectively, rule out residual disease. Ultrasound (US) or mammographically (MG) guided VAB will be used in this trial in order to detect residual tumor lesions in patients with radiological complete response (rCR) after NAC. The investigators will evaluate the diagnostic accuracy of the post-NAC VAB sample in comparison to the sample obtained in open surgery.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Vacuum assisted biopsy (VAB)

Detailed Description

Neoadjuvant chemotherapy (NAC), initially indicated to downstage tumors to achieve the option of breast conserving surgery, has lately become common practice in the primary treatment of breast cancer. The use of modern NAC regimens lead to a complete pathologic remission (pCR) of the tumor in more than 50% in aggressive tumor types.

In general, it is difficult to predict pCR in the absence of invasive surgical techniques, as it depends on several factors such as biological subtype, the used chemotherapy regimen and anatomic stage. The most common imaging methods beside clinical examination are breast ultrasound, mammography and breast magnetic resonance imaging (MRI). As NAC induces different response patterns, radiologic imaging is not sufficiently accurate in predicting residual disease. Because of this uncertainty, surgery (and the standardized assessment of resected tissue) is so far the only valid option to either ascertain complete response or to remove the complete residual disease.

Vacuum-assisted biopsy (VAB) with the possibility of obtaining tissue of the former tumor center could contribute more reliably to detect any residual tumor or respectively, rule out residual disease. Ultrasound (US) or mammographically (MG) guided VAB will be used in this trial in order to detect residual tumor lesions in patients with radiological complete response (rCR) after NAC. The investigators will evaluate the diagnostic accuracy of the post-NAC VAB sample in comparison to the sample obtained in open surgery.

The main objective of the trial is to determine the diagnostic accuracy of I-VAB using the full pathologic specimen evalutation obtained after open surgery to detect residual tissue.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel Tschopp; Phone Number: +41 44 387 9545; Email: daniel.tschopp@hirslanden.ch

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Not yet recruiting
    • Universitätsspital Salzburg
    • Contact: Andreas Sir; Phone Number: +43 572 555 74 34; Email: a.sir@salk.at
    • Contact: Andreas Sir, MD
  • Schwaz, Austria, 6130
    • Recruiting
    • Brustzentrum Schwaz
    • Contact: Michael Hubalek, MD; Phone Number: +43 5242 655 290; Email: office@dr-hubalek.at
    • Contact: Michael Hubalek, MD
  • Wien, Austria, 1130
    • Recruiting
    • St. Josef Krankenhaus Wien
    • Contact: Ulrich Schmidbauer, MD; Phone Number: +43 187 844 8200; Email: ulrich.schmidbauer@sjk-wien.at
    • Contact: Ulrich Schmidbauer, MD
• Germany
  • Frankfurt, Germany, 60431
    • Recruiting
    • Agaplesion Markus Krankenhaus
    • Contact: Marc Thill, Prof.; Phone Number: +49 69 9533 2228; Email: marc.thill@agaplesion.de
    • Contact: Marc Thill, Prof.
  • Heidelberg, Germany, 69121
    • Recruiting
    • Brustzentrum Heidelberg
    • Contact: Jörg Heil, Prof.; Phone Number: +49 6221 488 60 20; Email: joerg.heil@kse-hd.de
    • Contact: Joerg Heil, Prof.
  • Rostock, Germany, 18059
    • Recruiting
    • UFK Klinikum Südstadt Rostock
    • Contact: Steffi Hartmann, MD; Phone Number: +49 381 4401 47 00; Email: steffi.hartmann@kliniksued-rostock.de
    • Contact: Steffi Hartmann, MD
  • Wuppertal, Germany, 42283
    • Recruiting
    • Helios Universitätsklinikum Wuppertal
    • Contact: Vesna Bjelic-Radisic, Prof.; Phone Number: +49 202 896 14 11; Email: vesna.bjelic-radisic@helios-gesundheit.de
    • Contact: Vesna Bjelic-Radisic, Prof.
• Switzerland
  • Aarau, Switzerland, 5000
    • Recruiting
    • Tumor Zentrum Aarau
    • Contact: Andreas Jakob, MD; Phone Number: +41 62 836 78 30; Email: andreas.jakob@tumor-zentrum.ch
    • Contact: Andreas Jakob, MD
  • Baden, Switzerland, 5404
    • Recruiting
    • Kantonsspital Baden
    • Contact: Cornelia Leo, Prof; Phone Number: +41 56 486 35 14; Email: cornelia.leo@ksb.ch
    • Contact: Cornelia Leo, Prof
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitätsspital Basel
    • Contact: Christian Kurzeder, Prof; Phone Number: +41 61 328 79 90; Email: Christian.kurzeder@usb.ch
    • Contact: Christian Kurzeder, Prof
  • Basel, Switzerland
    • Recruiting
    • St. Claraspital
    • Contact: Roberto Rodriguez, MD; Phone Number: +41 61 685 34 53; Email: roberto.rodriguezrevuelto@claraspital.ch
    • Contact: Roberto Rodriguez, MD
  • Basel, Switzerland, 4052
    • Recruiting
    • Bethesda Spital
    • Contact: Dieter Müller, MD; Phone Number: +41 61 823 77 00; Email: dieter.müller@hin.ch
    • Contact: Dieter Müller, MD
  • Bern, Switzerland, 3013
    • Recruiting
    • Hirslanden Brustzentrum Bern Biel
    • Contact: Patrizia Sager, MD
    • Contact: Patrizia Sager, MD; Phone Number: +41 31 337 89 70; Email: patrizia.sager@hirslanden.ch
  • Chur, Switzerland, 7000
    • Recruiting
    • Kantonsspital Graubünden
    • Contact: Martina Gabriella Maranta, MD; Phone Number: +41 81 254 81 64; Email: martina.maranta@ksgr.ch
    • Contact: Martina Maranta, MD
  • Frauenfeld, Switzerland, 8501
    • Recruiting
    • Spital Thurgau AG Frauenfeld und Münsterlingen
    • Contact: Mathias Fehr, Prof; Phone Number: +41 52 723 72 55; Email: mathias.fehr@stgag.ch
    • Contact: Mathias Fehr, Prof
  • Genolier, Switzerland, 1272
    • Recruiting
    • Clinique de Genolier
    • Contact: Magdalena Kohlik, MD
    • Contact: Magdalena Kohlik, MD; Phone Number: +41 22 366 93 67; Email: mkohlik@genolier.net
  • Lugano, Switzerland, 6962
    • Recruiting
    • Ente Ospedaliero Cantonale, Dipartimento di ginecologia e ostretricia
    • Contact: Maria Luisa Gasparri, Prof.; Phone Number: +41 91 811 61 54; Email: marialuisa.gasparri@eoc.ch
    • Contact: Maria Luisa Gasparri, Prof.
  • Luzern, Switzerland, 6000
    • Recruiting
    • Luzerner Kantonsspital
    • Contact: Kathrin Schwedler, MD; Phone Number: +41 41 205 12 36; Email: kathrin.schwedler@luks.ch
    • Contact: Kathrin Schwedler, MD
  • Luzern, Switzerland, 6006
    • Recruiting
    • Hirslanden Klinik St. Anna
    • Contact: Peter Dubsky, Prof; Phone Number: +41 41 208 37 54; Email: peter.dubsky@hirslanden.ch
    • Contact: Peter Dubsky, Prof
  • Rheinfelden, Switzerland, 4310
    • Recruiting
    • Brustzentrum Rheinfelden
    • Contact: Maik Hauschild, MD; Phone Number: +41 61 835 62 20; Email: maik.hauschild@gzf.ch
    • Contact: Maik Hauschild, MD
  • St. Gallen, Switzerland, 9007
    • Recruiting
    • Kantonsspital St. Gallen
    • Contact: Christine Strub, MD; Phone Number: +41 71 494 97 14; Email: christine.strub@kssg.ch
    • Contact: Christine Strub, MD
  • St. Gallen, Switzerland, 9016
    • Recruiting
    • Tumor- und Brustzentrum Ostschweiz
    • Contact: Michael Knauer, Prof; Phone Number: +41 71 552 33 33; Email: michael.knauer@tbz-ost.ch
    • Contact: Michael Knauer, Prof
  • Winterthur, Switzerland, 8401
    • Recruiting
    • Kantonsspital Winterthur
    • Contact: Denise Vorburger, MD; Phone Number: +41 52 266 31 73; Email: denise.vorburger@ksw.ch
    • Contact: Denise Vorburger, MD
  • Zuerich, Switzerland, 8091
    • Recruiting
    • Universitäts Spital Zürich
    • Contact: Heike Frauchiger-Heuer, MD; Phone Number: +41 44 255 42 37; Email: heike.frauchiger-heuer@usz.ch
    • Contact: Heike Frauchiger-Heuer, MD
  • Zürich, Switzerland, 8008
    • Recruiting
    • Brust-Zentrum Seefeld
    • Contact: Christoph Tausch, MD; Phone Number: +41 44 533 81 00; Email: c.tausch@brust-zentrum.ch
    • Contact: Christoph Tausch, MD
• United Arab Emirates
  • Dubai, United Arab Emirates
    • Recruiting
    • Mediclinic City Hospital Dubai
    • Contact: Annett Al-Hamadi, MD; Phone Number: +971 4555 9112; Email: annett.hamadi@mediclinic.ae
    • Contact: Annett Al Hamadi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
• unifocal, histologically confirmed invasive breast cancer with IHC luminal B (with or without overexpression or amplification of the HER2 receptor) and all ER negative (ER < 10%) breast cancers
• Initial tumor size larger than 1 and less than 5 cm (cT1c to cT2), any N, M0
• Clipping of the primary tumor center prior to the start of neo-adjuvant chemotherapy
• Neo-adjuvant chemotherapy resulting in a radiological complete response or near complete response on MR-Imaging (confirmed within 28 days before or on registration) as described in the trial specific MR-Imaging instructions (available on the welcome page of the study specific SecuTrial link). MRI is strongly recommended, alternative ultrasound
• Former tumor bed must be accessible for biopsy
• Female or male aged ≥ 18 years
• Adequate condition for breast cancer surgery
• Patients with a previously treated malignancy are eligible, when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low

Exclusion criteria:

• Metastatic breast cancer
• Multifocal/Multicentric breast cancer
• Inflammatory breast cancer
• Luminal-A types of breast cancers (ER ≥ 10% and PgR ≥ 10 % and G1 or 2, and/or Ki-67 ≤ 20%, HER2 negative) or low risk if assessed by a validated genomic prognostic test (e.g. Mammaprint, Endopredict, Oncotype or Nanostring)
• Distinct radiological sign of residual disease in the breast after neo-adjuvant chemotherapy by imaging
• Intra-/peritumoral microcalcifications larger than 2 cm at time of diagnosis
• Any local therapy (irradiation or surgery) to the currently treated breast prior to the trial intervention
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, trial intervention and follow-up, affect patient compliance or place the patient at high risk from trial intervention-related complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; Unicentric histologically confirmed invasive luminal B, HER2- enriched, triple negative breast cancer + Clipping + Neoadjuvant chemotherapy; rCR / near-rCR in MRI / US; Registration; US-guided VAB; Breast conserving surgery / mastectomy; Pathology examination 1. Preoperative VAB, 2. Surgical specimen	Procedure: Vacuum assisted biopsy (VAB); The trial intervention consists of a diagnostic interventional procedure, US-guided or mammographically guided VAB post-NAC, prior to the standard breast surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	Sensitivity of I-VAB is defined as proportion of true positive patients (Both VAB and surgery showing non pCR) given patients with non pCR assessed using surgical specimen.	max. 6 weeks after registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical lymph node status	Surgical lymph node status (positive vs. negative) is categorized by the pathologist according to surgical specimen.	max. 6 weeks after registration
Adverse events	Proportion of patients with bleeding/hematoma causing immediate surgical intervention and breast infection, which are related to VAB.	From US-guided VAB (max. 6 weeks after registration) until 2 weeks after breast surgery (max 1 day after VAB).
Specificity	Specificity of I-VAB is defined as proportion of true negative patients (Both VAB and surgery showing pCR) given patients with pCR assessed using surgical specimen.	max. 6 weeks after registration
Positive predictive value (PPV)	PPV of I-VAB is defined as proportion of true positive patients given patients with non pCR assessed using VAB	max. 6 weeks after registration
Negative predictive value (NPV)	NPV of I-VAB is defined as proportion of true negative patients given patients with pCR assessed using VAB	max. 6 weeks after registration
Accuracy (ACC)	ACC of I-VAB is defined as the proportion of true positive and true negative patients.	max. 6 weeks after registration

Collaborators and Investigators

• Sponsor: Klinik Hirslanden, Zurich
• Collaborators: Oncoplastic Breast Consortium (OPBC)
• Investigators: Study Chair: Christoph Tausch, MD, Brust-Zentrum, Zürich

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; Neoadjuvant chemotherapy; VISION I; Vacuum assisted biopsy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HIRSLANDEN 01 OPBC SAKK 23/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No