Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer (RESPONDER)

March 23, 2020 updated by: Jörg Heil, Heidelberg University

RESPONDER Trial - Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer

The main purpose of the study is to evaluate the potential of a minimal invasive, vacuum-assisted biopsy (VAB) to reliably diagnose a pathological complete response (pCR) in the breast after neoadjuvant chemotherapy (NACT) in breast cancer patients.

The study is designed as a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial, in which we aim to confirm the applicability of preoperative VAB in patients after NACT. Furthermore, we aspire to quantify the rate of concordant pathological findings (pCR yes / no) in biopsy and surgical specimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In clinical routine surgical treatment follows the pre-operative chemotherapy (NACT). However, recent studies have demonstrated that shrinking tumors need less surgical treatment indicating that patients with pCR could potentially be spared of surgery in the future. However, up to now, prediction of pCR after NACT is only moderately accurate. This prospective, monocenter diagnostic trial aims to explore if minimal invasive biopsies (MIB) might overcome this diagnostic challenge.

Ultrasound guided VAB will be performed on 600 breast cancer patients after NACT and directly prior to surgery.

There are only two trial visits that are specific to the trial. All other visits will be routine visits.

  1. The first trial visit will take place in order to provide the patient with detailed information on the study, its' aims, the VAB procedure, and its risks. The patient will be asked to sign a form of informed consent.

  2. At the second trial visit the performance of the VAB (=index test) will take place. This trial visit may vary by patient, tumor, and trial site characteristics and may either be:

    1. An ultrasound guided VAB or
    2. A stereotactically / mammographically guided VAB. All possible VAB procedures and settings (in outpatient clinic, or in operating room directly before the surgery) are equally accepted. We will allow every trial site to choose the adequate setting to the trial site´s and to their patients' needs.

A visit for a follow up will not be necessary in this setting. Possible complications of the VAB procedure may occur while the biopsy is taken.

The pathological results of the VAB specimen will be generally categorized as follows:

  1. Residual tumor cells in VAB specimen (=non-pCR)
  2. No residual tumor cells in the VAB specimen and VAB representative of former tumor region (="pCR in VAB")
  3. No residual tumor cells in the VAB specimen but VAB unclear or not representative of former tumor region (=possible sampling error). These VABs are categorized as uninformative for the primary endpoint of the clinical trial.

The results will be compared to those of the pathological examination of surgical specimen.

Study Type

Interventional

Enrollment (Actual)

452

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Baden-Württemberg
      • Heidelberg, Baden-Württemberg, Germany, 69120
        • University Breast Unit, Department of Gynecology, University of Heidelberg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria

  • Female patients with primary breast cancer after Neoadjuvant Chemotherapy (NACT) treatment which has been performed for at least 12 weeks and resulted in cPR or cCR (see below).
  • >/=18 years
  • any cT and cN stage, except cT4 stages
  • any routine breast cancer surgical intervention planned according to guidelines (breast conservation or mastectomy)
  • Residual intramammary target lesion or clip marker is visible in ultrasound and / or mammography
  • Diagnosis of imaging complete or partial response according to RECIST 1.1 by at least mammography or ultrasound, according to local routine)
  • Inclusion of only one breast per patient, in bilateral cancer one breast can be included
  • In case of multicentric disease: confirmation of the same tumorbiological subtype defined by immunohistology in at least 2 lesions.
  • Ability of subject to understand character and individual consequences of the clinical trial.
  • Written informed consent (must be available before enrolment in the trial).

Exclusion Criteria

  • Palliative or recurrent breast cancer
  • in case of clip marker = target lesion: dislocation of marker (>5mm distance to the initial lesion border at the time of clip placement)
  • contraindication for VAB or associated procedures (e.g. local anesthesia)
  • Pregnancy and lactation
  • held in an institution by legal or official order
  • legally incapacitated.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: single-arm study
This project is designed as a one-armed diagnostic study. Every patient included in the study will undergo the same diagnostic test, the vacuum-assisted biopsy, after NACT and before surgery according to guidelines.
Device: Vacuum-Assisted Biopsy
The vacuum-assisted (7-10G), minimal invasive biopsy (VAB), either guided by ultrasound, or by mammography (stereotaxy) during the second trial visit (V2) will be performed once. In analogy to the German S3 guideline on primary breast cancer management we recommend to take at least 12 biopsies with 10G needles or less in case of larger needle sizes.
Other Names:
  • minimal invasive biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
false negative VAB results, reported as the false negative rate (= FNR)
Time Frame: after breast surgery, up to 6 weeks after VAB
non-detected residual tumor by VAB (=index test) compared to breast surgery (=reference test): FNR = rate of patients with non-detected residual tumor by VAB compared to breast surgery Residual tumor is defined as a positive result; in surgical specimen as well as in VAB.
after breast surgery, up to 6 weeks after VAB

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
negative predictive value (NPV)
Time Frame: after breast surgery, up to 6 weeks after VAB

The negative predictive value (NPV) will be calculated as the quotient of the number of cases with pCR in VAB and in surgical specimen (= true negative result), divided by the total number of cases with pCR in VAB.

Residual tumor is defined as a positive result; in surgical specimen as well as in VAB.
after breast surgery, up to 6 weeks after VAB
positive predictive value (PPV)
Time Frame: after breast surgery, up to 6 weeks after VAB

The positive predictive value (PPV) will be calculated as the number of biopsies with detected residual tumor cells in VAB and surgery (= true positive results) divided by the number of all cases with residual tumor cells in the VAB.

Residual tumor is defined as a positive result; in surgical specimen as well as in VAB.
after breast surgery, up to 6 weeks after VAB
false positive rate (FPR)
Time Frame: after breast surgery, up to 6 weeks after VAB
FNR = rate of patients with falsely diagnosed residual tumor by VAB compared to breast surgery Residual tumor is defined as a positive result; in surgical specimen as well as in VAB.
after breast surgery, up to 6 weeks after VAB

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heidelberg University

Collaborators

German Research Foundation

Investigators

  • Principal Investigator: Joerg Heil, Professor, University of Heidelberg University Breast Unit, Department of Gynecology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2017

Primary Completion (Actual)

May 24, 2019

Study Completion (Actual)

September 15, 2019

Study Registration Dates

First Submitted

October 16, 2016

First Submitted That Met QC Criteria

October 26, 2016

First Posted (Estimate)

October 28, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2020

Last Update Submitted That Met QC Criteria

March 23, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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