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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Sensitivity [Time frame: max. 6 weeks after registration]

Secondary outcome measures (6)

• Specificity [Time frame: max. 6 weeks after registration]
• Positive predictive value (PPV) [Time frame: max. 6 weeks after registration]
• Negative predictive value (NPV) [Time frame: max. 6 weeks after registration]
• Accuracy (ACC) [Time frame: max. 6 weeks after registration]
• Surgical lymph node status [Time frame: max. 6 weeks after registration]
• Adverse events [Time frame: From US-guided VAB (max. 6 weeks after registration) until 2 weeks after breast surgery (max 1 day after VAB).]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Diagnostic

Study locations

Switzerland · 18 centers

• Tumor Zentrum Aarau — Aarau
• Kantonsspital Baden — Baden
• Universitätsspital Basel — Basel
• Bethesda Spital — Basel
• St. Claraspital — Basel
• Hirslanden Brustzentrum Bern Biel — Bern
• Kantonsspital Graubünden — Chur
• Spital Thurgau AG Frauenfeld und Münsterlingen — Frauenfeld
• … and 10 more centers

Germany · 4 centers

• Agaplesion Markus Krankenhaus — Frankfurt
• Brustzentrum Heidelberg — Heidelberg
• UFK Klinikum Südstadt Rostock — Rostock
• Helios Universitätsklinikum Wuppertal — Wuppertal

Austria · 3 centers

• Universitätsspital Salzburg — Salzburg
• Brustzentrum Schwaz — Schwaz
• St. Josef Krankenhaus Wien — Vienna

United Arab Emirates · 1 center

• Mediclinic City Hospital Dubai — Dubai

Identifiers

NCT: NCT04289935 · HIRSLANDEN 01 OPBC SAKK 23/18

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗