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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02948764
Recruitment Status : Completed
First Posted : October 28, 2016
Last Update Posted : March 25, 2020
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Jörg Heil, Heidelberg University

Tracking Information
First Submitted Date  ICMJE October 16, 2016
First Posted Date  ICMJE October 28, 2016
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE March 8, 2017
Actual Primary Completion Date May 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2016)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer
Official Title  ICMJE RESPONDER Trial - Diagnosis of Pathological Complete Response by Vacuum-assisted Biopsy After Neoadjuvant Chemotherapy in Breast Cancer
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE 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 Name: minimal invasive biopsy
Study Arms  ICMJE 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.
Intervention: Device: Vacuum-Assisted Biopsy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2020)
452
Original Estimated Enrollment  ICMJE
 (submitted: October 26, 2016)
600
Actual Study Completion Date  ICMJE September 15, 2019
Actual Primary Completion Date May 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02948764
Other Study ID Numbers  ICMJE 2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Jörg Heil, Heidelberg University
Study Sponsor  ICMJE Heidelberg University
Collaborators  ICMJE German Research Foundation
Investigators  ICMJE
Principal Investigator: Joerg Heil, Professor University of Heidelberg University Breast Unit, Department of Gynecology
PRS Account Heidelberg University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP