Intelligent Vacuum Assisted Biopsy Immediately Before Surgery as an Intra- or Pre-Operative Surrogate for Patient Response to Neoadjuvant Chemotherapy for Breast Cancer

Breast Cancer Clinical Trial

— VISION I  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04289935
• Other study ID #: HIRSLANDEN 01 SAKK 23/18
• Status: Recruiting
• Phase: N/A
• Start date: August 17, 2020
• Est. completion date: June 2025

Study information

• Verified date: January 2023
• Source: Klinik Hirslanden, Zurich
• Contact: Daniel Tschopp
• Phone: +41 44 387 9545
• Email: daniel.tschopp[@]hirslanden.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures

• unifocla, 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)

• 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 in MRI

• 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

• Contraindication for MRI

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Switzerland	Tumor Zentrum Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Bethesda Spital	Basel
Switzerland	St. Claraspital	Basel
Switzerland	Universitätsspital Basel	Basel
Switzerland	Hirslanden Brustzentrum Bern Biel	Bern
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Spital Thurgau AG Frauenfeld und Münsterlingen	Frauenfeld
Switzerland	Clinique de Genolier	Genolier
Switzerland	Hirslanden Klinik St. Anna	Luzern
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Brustzentrum Rheinfelden	Rheinfelden
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Tumor- und BrustZentrum Ostschweiz	St. Gallen
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Brust-Zentrum Seefeld	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Klinik Hirslanden, Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Accuracy (ACC)	ACC of I-VAB is defined as the proportion of true positive and true negative patients.	max. 6 weeks after registration
Secondary	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
Secondary	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).