Trial document





This trial has been registered retrospectively.
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  DRKS00004414

Trial Description

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Title

HYbrid Knife in Bladder Cancer Resection
Initially Detected by Hexvix based
BLUe-Light Enhancement

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Trial Acronym

HybridBlue

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URL of the Trial

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Brief Summary in Lay Language

Background:

Endoscopic transurethral resection of the bladder (TURB) is the gold standard for diagnosis and therapy of bladder cancer. The resection is commonly done using a wire-loop.
With this, visible tumour tissue is removed and investigated by the pathologist. The complete resection of the tumour is of crucial importance for the further course of the disease.
One major drawback of this approach is that en-bloc resection is only possible for tumours smaller than the loop-diameter; larger tumours have to be resected step by step in pieces (“piecemeal resection”). This contradicts the oncological principle which means that any unnecessary handling and fragmentation of tumour tissue should be avoided to minimize the risk of tumour seeding. Furthermore, piecemeal resection hampers accurate and reliable histopathological evaluation which complicates diagnosis and targeted therapy.

A similar situation concerning the therapy of gastrointestinal cancer has led to the development of a technique called endoscopic submucosal dissection “ESD”. Briefly explained the key steps of the resection are: Marking the lesion, elevating the tumour by injecting saline fluid in the connective tissue under the mucosa (this fluid cushion serves as protection against perforation), circumferentially incising the lesion and finally resecting the tumour en-bloc by dissecting through the submucosa. This technique allows en-bloc resection of lesions bigger than 2cm in gastroenterology and has led to lower rates of residual tumours and recurrence rates.
All resection-steps can be done with the HybridKnife®, an endoscopic instrument combining a radiofrequency probe with a waterjet.

Study objectives:
The first goal of the HybridBlue- study is to compare two endoscopic resection techniques (wire loop / HybridKnife®) with regard to completeness of resection, pathological validity and significance of the resected specimen.
After follow-up, the recurrence- and progression data of the two study groups will be documented and compared.

Study participants:
Adults of both genders with a suspected diagnosis of a non-muscle invasive bladder tumour (initial diagnosis or recurrence).

Procedure:
Study participants will be randomly grouped to one of the resection technique described above (wire-loop or HybridKnife). Based on first results, the two methods do not differ in surgical risks, although there is a possible lower risk of perforations (small hole in the bladder) during the resection with the HybridKnife.
We expect a more valuable pathological evaluation and the en-bloc resection may result in less tumour seeding. The subsequent therapy and the follow-up are in line with the clinical routine and urological guidelines.
For the participant the study ends with cystoscopy after 12 months.

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Brief Summary in Scientific Language

Background:
Endoscopic transurethral resection of the bladder (TURB) is the gold standard for diagnosis and therapy of nonmuscle invasive bladder cancer (NMIBC). The resection is commonly done using a wire-loop.

As a result, en-bloc resection is only possible for tumours smaller than the loop-diameter, larger tumours have to be resected in pieces (“piecemeal resection”), which contradicts oncological principles and hampers accurate and reliable histopathological evaluation
A similar situation concerning the therapy of gastrointestinal cancer has led to the development of a technique called “ESD”, endoscopic submucosal dissection. Briefly explained the key steps of the resection are: Marking the lesion, elevating the tumour by injecting saline fluid in the submucosa to avoid perforation, circumferentially incising the lesion and finally resecting the tumour en-bloc by dissecting through the submucosa. This technique allows en-bloc resection of lesions > 2cm in gastroenterology.
All resection-steps can be done with the HybridKnife®, an endoscopic instrument combining a RF-probe with a waterjet. The technique has been adopted to remove NMIBC and feasibility, security and capacity of resecting tumours much larger than the size of wire-loops en-bloc has been shown in two clinical studies.

Study objectives:
The first goal of the HybridBlue- study is to compare two endoscopic resection techniques (wire loop / HybridKnife®) with regard to pathological validity and meaningfulness of the resected specimen.
In the HybridKnife®-group we expect an improvement in the assessment of the depth of both the horizontal and lateral tumour infiltration, a definite decision concerning the R0-status, and a more reliable substaging of T1-tumours.
Secondly, in case a second TURB after 2-6 weeks is needed, we expect a lower rate of tumour cells in the specimen in the HybridKnife group (less residual tumour after HybridKnife resection).
After follow-up, the recurrence- and progression data of the two study groups will be documented and compared. The data will be used to calculate the sample size for a study in which recurrence- and progression rate after HybridKnife TURB could be investigated.

A critical factor for the completeness of the resection of a NMI bladder tumour is the reliable demarcation of the tumour from the surrounding, healthy tissue, especially in the incidence of CIS. To achieve this, PDD with Hexvix® (IPSEN) will be used, first for the detection of the tumour, and after resection to control the completeness of the removal. A second PDD-cystoscopy will be conducted at the end of the follow-up (after 12 months).
Additional analysis concerning histopathological effects of Hexvix® are planned: In-toto specimen of the HybridKnife®-group will be used to collect data firstly about Hexvix® tissue penetration and secondly to correlate the spatial expansion of fluorescent marked tissue and tumour-specific histological findings in the cross-sections.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00004414
  •   2012/11/07
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  •   yes
  •   Approved
  •   220/2012BO1, Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen
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Secondary IDs

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Health Condition or Problem studied

  •   C67 -  Malignant neoplasm of bladder
  •   D09.0 -  Carcinoma in situ: Bladder
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Interventions/Observational Groups

  •   TURB, resection with wire loop
  •   TURB, resection with HybridKnife
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Proportion of specimen which can be reliably evaluated pathologically concerning muscle-invasiveness. Data will be gathered on e-questionnaires

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Secondary Outcome

Percentage of en-bloc resections
Number each group of proven R0-status
In case of Re-TURB: Percentage of tumour-free Re-TURB specimen
Percentage of specimen of T1-tumours for which an histological subclassification was possible
Determination of Hexvix® tissue penetration
Correlation of the spatial expansion of fluorescent marked tissue and tumour-specific histological findings in the cross-sections
Data collection: All resected specimen will be investigated by the study-pathologist, data will be gathered on e-questionnaires.

After 12 months a PDD-cystoscopy will be conducted, recurrence and progression rate will be documented on e-questionnaires.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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

  •   Actual
  •   2012/09/27
  •   120
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Non muscle-invasive bladder cancer
Diagnosed by cystoscopy, imaging technique or cytology
min. 1 lesion > 0,5 cm

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Exclusion Criteria

- Age under 18 years.
- Persons who are incapable of giving consent.
- Pregnancy.
- Muscle-invasive cancer.
- Multifocal cancer > 5 lesions exceeding 0,5 cm
- Tumours which could not be resected completely with both methods (due to technical problems).
- Tumours too big to be retrieved endoscopically in one piece.
- In case of spacious CIS: Tumours which cannot be completely removed endoscopically
- Recent (6-8 weeks) instillation therapy (chemotherapeutics, BCG)
- pronounced fibrosis of the bladder (contracted bladder)
- Patients who will be treated with early installation therapy

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Addresses

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    • Universitätsklinikum Tübingen Universitätsklinik für Urologie
    • Mr.  Prof. Dr. med  Arnulf  Stenzl 
    • Hoppe-Seyler-Str. 3
    • 72076  Tübingen
    • Germany
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    • Universitätsklinikum Tübingen Universitätsklinik für Urologie
    • Mr.  Prof. Dr. med  Arnulf  Stenzl 
    • Hoppe-Seyler-Str. 3
    • 72076  Tübingen
    • Germany
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    • Universitätsklinikum Tübingen Universitätsklinik für Urologie
    • Mr.  Prof. Dr. med  Arnulf  Stenzl 
    • Hoppe-Seyler-Str. 3
    • 72076  Tübingen
    • Germany
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    • Klinik für Urologie der Universität Regensburg Caritas-Krankenhaus St. Josef
    • Mr.  Dr. med.  Hans-Martin  Fritsche 
    • Landshuter Str. 65
    • 93053  Regensburg
    • Germany
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    • Urologische Universitätsklinik Erlangen Waldkrankenhaus St. Marien
    • Mr.  Prof. Dr. med.  Bernd  Wullich 
    • Rathsbergerstrasse 57
    • 91054  Erlangen
    • Germany
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    • Klinikum der Universität München Klinikum Großhadern Urologische Klinik und Poliklinik
    • Mr.  PD Dr. med.  Alexander  Karl 
    • Marchioninistraße 15
    • 81377  München
    • Germany
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    • Charité - Universitätsmedizin BerlinCC 8: Chirurgische MedizinKlinik für Urologie
    • Mr.  Prof. Dr. med  Kurt  Miller 
    • Hindenburgdamm 30
    • 12200  Berlin
    • Germany
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    • Urologische KlinikDiakonissenkrankenhaus und Paulinenhilfe gGmbH Akademisches Lehrkrankenhaus der Universität Tübingen
    • Mr.  Dr. med.  Jens  Mundhenk 
    • Rosenbergstraße 38
    • 70176  Stuttgart
    • Germany
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Sources of Monetary or Material Support

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    • ERBE Elektromedizin GmbH
    • Waldhoernlestraße 17
    • 72072  Tuebingen
    • Germany
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    • Ipsen Pharma GmbH
    • Willy-Brandt-Straße 3
    • 76275  Ettlingen
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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