Trial document




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  DRKS00011761

Trial Description

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Title

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

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Trial Acronym

[---]*

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URL of the Trial

http:///

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Brief Summary in Lay Language

Chemotherapy before surgery (=neoadjuvant chemotherapy, NACT) is nowadays a standard therapeutical approach in many breast cancer cases. Due to improved medicines, many tumors respond increasingly well to this therapy. Thus, chemotherapy even leads to a complete eradication of the tumor (= pathological complete response, pCR) with increasing frequency.

Unfortunately, it is still not possible to diagnose such a complete tumor remission after the neoadjuvant chemotherapy and before surgery. At present, surgery is therefore indispensable for a reliable diagnosis. However, the question arises whether surgery is still necessary for the therapy of the cancer in cases of complete tumor remission. In order to study this question further, another reliable, diagnostic method needs to be developed.

We carried out different studies on this subject at the Department of Gynecology of the University Hospital Heidelberg. Those showed exceptionally good results for the so-called vacuum-assisted biopsy. We now aim to confirm those preliminary results in a national trial including 600 patients. According to the study design, a vacuum-assisted biopsy will be performed on participants after neoadjuvant chemotherapy and before surgery. As we aim to evaluate the diagnostic accuracy of the vacuum-assisted biopsy, the resulst of the histopathological evaluation of the biopsy specimen will be compared to the results of the evaluation of the surgical specimen.

Potential participants of the study are patients with breast cancer treated by neoadjuvant chemotherapy and showing either complete or partial response in clinical examination.

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Brief Summary in Scientific Language

Chemotherapy before surgery (=neoadjuvant chemotherapy, NACT) is increasingly used in breast cancer treatment. Moreover, a pathological complete response (pCR) in the breast (=ypT0), meaning that no tumor cells are present after NACT, is achieved with increasing frequency. This scenario provokes the widely debated issue if local treatment (surgery and / or radiotherapy) is actually beneficial in patients with pCR. Should those procedures prove not to serve any therapeutic purpose, patients deserve to be spared its’ potential, negative effects.

However, before this question regarding the therapeutic benefit of local treatment can be investigated, it is essential that a reliable diagnosis of a pCR is possible without the histopathological evaluation of the surgical specimen. Up to date, imaging methods as ultrasound, mammography, or breast MRI do not provide us with a valid prediction of a pCR.

This multicenter, confirmative, clinical trial aims to confirm that a pCR after NACT can be validly diagnosed by using vacuum-assisted, minimal invasive biopsy techniques (VAB). The VAB will be performed after NACT and before standard surgical treatment. The study will include 600 patients with at least partial response in breast imaging in order to confirm that less than 5% of the patients with a residual after NACT are falsely classified as having no residual tumor (=pCR) by the VAB.

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Organizational Data

  •   DRKS00011761
  •   2017/02/20
  •   2016/10/30
  •   yes
  •   Approved
  •   S-264/2016, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

  •   NCT02948764  (clinicaltrials.gov)
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Health Condition or Problem studied

  •   C50.0 -  Malignant neoplasm: Nipple and areola
  •   C50.8 -  Malignant neoplasm: Overlapping lesion of breast
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Interventions/Observational Groups

  •   single arm study: the vacuum assisted biopsy (VAB, = index test) as well as the surgery (=reference test) will both be performed on every patient
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Characteristics

  •   Interventional
  •   [---]*
  •   Other
  •   Blinded
  •   assessor
  •   Other
  •   Diagnostic
  •   Other
  •   N/A
  •   No
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Primary Outcome

Primary endpoint is the false negative rate (=FNR). The false negative rate (FNR) will be calculated as the quotient of the number of cases with “pCR in VAB” and residual tumor in surgical specimen (false negative VAB results), divided by the total number of cases with residual tumor in surgical specimen in the cohort of the confirmatory primary outcome analysis. The primary endpoint will be assessed the pathologic report (comparison of pathologic result of the biopsy with the pathological result of surgical specimen).

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Secondary Outcome

Negative predictive value (NPV), positive predictive value (PPV), sensitivity, specificity. The secondary endpoints will be analysed descriptively for the whole cohort and different subgroups: (1) Tumor biology, (2) clinical response, (3) assessment of representiveness, (4) trial sites, (5) guidance method (mammography / ultrasound).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2017/03/08
  •   600
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
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Additional 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)

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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

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Addresses

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    • Universitätsklinikum Heidelberg
    • Im Neuenheimer Feld 672
    • 69120  Heidelberg
    • Germany
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    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
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    • Brustzentrum der Universitätsfrauenklinik Heidelberg
    • Mr.  Professor  Jörg  Heil 
    • Im Neuenheimer Feld 440
    • 69120  Heidelberg
    • Germany
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    • Brustzentrum der Universitätsfrauenklinik Heidelberg
    • Mr.  Professor  Jörg  Heil 
    • Im Neuenheimer Feld 440
    • 69120  Heidelberg
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting stopped after recruiting started
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.