Clinical trial NCT04289935: Intelligent Vacuum Assisted Biopsy Immediately Before Surgery As an Intra- or Pre-Operative Surrogate for Patient Response to Neoadjuvant Chemotherapy for Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Neoadjuvant chemotherapy
VISION I
breast cancer
Vacuum assisted biopsy
Lead sponsor: Klinik Hirslanden, Zurich
Sponsor class: OTHER
Collaborators: name: Oncoplastic Breast Consortium (OPBC)
First posted: 2020-02-28
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: multicenter, prospective, single arm, feasibility trial
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity
timeFrame: max. 6 weeks after registration
Secondary outcomes:
measure: Specificity
timeFrame: max. 6 weeks after registration
measure: Positive predictive value (PPV)
timeFrame: max. 6 weeks after registration
measure: Negative predictive value (NPV)
timeFrame: max. 6 weeks after registration
measure: Accuracy (ACC)
timeFrame: max. 6 weeks after registration
measure: Surgical lymph node status
timeFrame: max. 6 weeks after registration
measure: Adverse events
timeFrame: From US-guided VAB (max. 6 weeks after registration) until 2 weeks after breast surgery (max 1 day after VAB).
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Universitätsspital Salzburg
city: Schwaz
country: Austria
facility: Brustzentrum Schwaz
city: Wien
country: Austria
facility: St. Josef Krankenhaus Wien
city: Frankfurt
country: Germany
facility: Agaplesion Markus Krankenhaus
city: Heidelberg
country: Germany
facility: Brustzentrum Heidelberg
city: Rostock
country: Germany
facility: UFK Klinikum Südstadt Rostock
city: Wuppertal
country: Germany
facility: Helios Universitätsklinikum Wuppertal
city: Aarau
country: Switzerland
facility: Tumor Zentrum Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Basel
country: Switzerland
facility: Bethesda Spital
city: Basel
country: Switzerland
facility: St. Claraspital
city: Bern
country: Switzerland
facility: Hirslanden Brustzentrum Bern Biel
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Frauenfeld
country: Switzerland
facility: Spital Thurgau AG Frauenfeld und Münsterlingen
city: Genolier
country: Switzerland
facility: Clinique de Genolier
city: Lugano
country: Switzerland
facility: Ente Ospedaliero Cantonale, Dipartimento di ginecologia e ostretricia
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Luzern
country: Switzerland
facility: Hirslanden Klinik St. Anna
city: Rheinfelden
country: Switzerland
facility: Brustzentrum Rheinfelden
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: St. Gallen
country: Switzerland
facility: Tumor- und BrustZentrum Ostschweiz
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zuerich
country: Switzerland
facility: Universitäts Spital Zürich
city: Zürich
country: Switzerland
facility: Brust-Zentrum Seefeld
city: Dubai
country: United Arab Emirates
facility: Mediclinic City Hospital Dubai
Study officials:
affiliation: Brust-Zentrum, Zürich
name: Christoph Tausch, MD
role: STUDY_CHAIR
References: