Trial document




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  DRKS00017724

Trial Description

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Title

Metastatic Melanoma Patients Under Immunotherapy: Monitoring of Therapeutic Success Using Liquid Biopsy and PET/CT in a Prospective Study

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Trial Acronym

MM_PET/CT+LB

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Patients with metastatic melanoma have had an extremely unfavorable prognosis. New immunotherapies (so-called checkpoint inhibitors) have significantly improved their chances of survival. Currently, therapeutic antibodies against CTLA-4 and PD-1 are combined as a so-called dual immune checkpoint blockade. The disadvantage of combined immunotherapy, however, is that it causes severe side effects in almost 60% of patients, often leading to interruption or early discontinuation of therapy. In cooperation with the regional health insurance companies, the prospective study presented here aims to obtain indications for an effective treatment regime for these very expensive immunotherapies that have many side effects. Therefore, it is necessary to reliably determine if there is already a good response to immunotherapy, justifiing a temporary therapy break.
Conventional imaging techniques are often insufficient to monitor immunotherapy. Therefore, functional data collected by positron emission tomography (PET) are used, which can map the metabolic activity of the tumors and allow a better indication of the response. Furthermore, the additional sampling of a so-called "liquid biopsy" (determination of various biomarkers from the blood) takes place for each therapy cycle.

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Brief Summary in Scientific Language

With the new immunotherapy, the so-called checkpoint inhibitors, the survival prospects of patients with metastatic melanoma have improved significantly. However, many studies have shown that assessing treatment responses as a result of immune system linked mechanisms is much more complex and difficult than with conventional cancer (chemo)therapies. This concerns in particular questions about a therapy break because of strong side effects and the duration of the immunotherapy altogether. Functional imaging methods such as PET/CT show clear advantages here. Also data on the tumor DNA in the blood, which are obtained through regular blood tests (so-called liquid biopsy), one hopes for statements on the response and the prognosis.
The cell-free circulating DNA (cfDNA) and in particular the circulating tumor DNA (ctDNA) are biomarkers that can be collected as part of a liquid biopsy. Studies in patients with malignant melanoma have already shown that BRAF mutation in ctDNA correlates with treatment response, clinical course, and risk of relapse under BRAF inhibitor therapy (Haselman et al., 2018). Similarly, the total amount of ccDNA in melanoma patients appears to be correlated with tumor burden and prognosis (Valpione et al., 2018).
With the help of liquid biopsies, we would like to additionally investigate in this study whether a response to treatment can be detected early on, or recurrence in the case of a therapy break, and whether these results correlate with the results of PET/CT.
This is particularly important because ipilimumab and nivolumab dual immune checkpoint blockade causes severe side effects in nearly 60% of patients, often forcing them to discontinue therapy after the first cycles of therapy. At this point in time, it is often necessary to reliably determine whether there is already a good response to immunotherapy and a temporary therapy break is warranted (e.g., lack of metabolic activity in the PET). In patients who have stable metastatic findings during their immunotherapy (despite the continuation of immunotherapy metastases are no longer shrinking), raises the question of tumor vitality. If there was a lack of or very little metabolic activity in PET/CT, a therapy break would be an option. After a break of about 3 months, it could then be determined by renewed PET/CT, if the tumor vitality has increased again (progress to PERCIST) or under Stable Disease (SD), the therapy break can be extended.

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Organizational Data

  •   DRKS00017724
  •   2019/08/01
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  •   yes
  •   Approved
  •   196/2019BO2, 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

  •   C43 -  Malignant melanoma of skin
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Interventions/Observational Groups

  •   Patients with unresectable malignant melanoma stage IV who undergo a dual immuno-checkpoint blockade with nivolumab and Ipilimumab (clinical indicated).
    Patients receive a FDG-PET/CT every 3 months, flanked by regular "liquid biopsies" for the analysis of various biomarkers from the blood.

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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Diagnostic
  •   Single (group)
  •   N/A
  •   No
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Primary Outcome

Optimizing the course of dual immunotherapy in patients with metastatic melanoma through improved therapy monitoring using liquid biopsies and PET/CT. Endpoint at completion of data collection and evaluation of data sets from 60 patients.

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Secondary Outcome

• Superiority of liquid biopsies to laboratory diagnostics LDH and S100
• Definition of decision support for possible treatment breaks based on liquid biopsies and/or PE /CT (patients with SD)
• Detection of recurrences during treatment breaks using liquid biopsies and/or PET/CT
• Development of a prognostic index of LB, PET/CT and mutation status, which can be used to support a therapy break in SD
(Endpoint at completion of data collection and evaluation of data sets from 60 patients)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/08/01
  •   60
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   100   Years
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Additional Inclusion Criteria

• unresectable malignant melanoma stage IV
• Age ≥18 years
• Indicated dual immunotherapy with nivolumab and ipilimumab
• PET/CT examinations for clinical indication before treatment initiation ("baseline staging") and for therapy control (3-monthly)
• at least one existing measurable lesion

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Exclusion Criteria

• non-consenting patients

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitäts-Hautklinik Tübingen
    • Ms.  Dr. med.  Andrea  Forschner 
    • Liebermeisterstr. 25
    • 72076  Tübingen
    • Germany
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    • Ms.  Prof. Dr.  Christina  Pfannenberg 
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    • Institut für Medizinische Genetik und Angewandte Genomik, Universitätsklinikum Tübingen
    • Mr.  Prof. Dr. med.  Olaf  Rieß 
    • Calwerstr. 7
    • 72076  Tübingen
    • Germany
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    • Universitäts-Hautklinik Tübingen
    • Ms.  Dr. med.  Andrea  Forschner 
    • Liebermeisterstr. 25
    • 72076  Tübingen
    • Germany
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    • Universitäts-Hautklinik Tübingen
    • Ms.  Dr. med.  Andrea  Forschner 
    • Liebermeisterstr. 25
    • 72076  Tübingen
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Tübingen
    • Geissweg 3
    • 72076  Tübingen
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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