Trial document




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  DRKS00010162

Trial Description

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Title

Test-Retest-Reliability and Tumor-Localisation-Dependent Sensitivity of Neurocognitive Tests in Glioblastoma Patients. A prospective multicentric study.

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Trial Acronym

ReCog-GBM-L

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URL of the Trial

http://neurochirurgie.uk-koeln.de/de/neurochirurgie/forschung/klinische-forschung/klinische-arbeitsgruppen/ag-funktionelle-bildgebung

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Brief Summary in Lay Language

Brain tumours are often associated with neurocognitive deficits. Recent studies showed a high impact of neurocognitive deficits on health-related quality of life. Moreover, neurocognitive function can serve as a strong independent predictor for survival of brain tumour patients. Worsening of neurocognitive functions may even allow to detect tumour recurrencies / progression. Additional therapy such as radiotherapy or chemotherapy can influence neurocognitive functions, depending on the treatment form and dose / intensity.
Thus, investigating neurocognitive functions in brain tumour patients is highly interesting and can improve the management of those patients. However, there is no consensus regarding a practicable neurocognitive test battery for brain tumor patients available for German-speaking patients until now. Moreover, shorter test batteries specifically adapted for distinct brain tumour regions are needed, especially to allow time-efficient individual follow-up testing.
We, therefore, conduct a prospective evaluation of a novel test battery, which covers all crucial neurocognitive functions and requires roughly 45 min testing time and is paper-based.
Therefore, 192 patients with newly diagnosed monolocular, supratentorial contrast-enhancing brain tumours shall be allocated to the study (N=128: tumor resection; N=64: stereotactic biopsy). 12 university / teaching hospitals have provided written agreement to participate in this multicentric study.
The participation in the study does not influence the tumour treatment at all. During the patients' regular stay in the hospital (for tumour surgery), neurocognitive testing will take place once before and twice on consecutive days (day 3-7) after surgery. Moreover, follow-up testing is planned once at the time of the regular outpatients visits 3 months after surgery (+/- 4 weeks).

Aims of the study are: (1) investing the effect of surgery (as compared to biopsy) and (2) the effect of concomitant radiochemotherapy (3-months-follow-up) on neurocognitive functioning; (3) measure the retest reliability of the test battery; (4) compare the neurocognitive test data with the individual MRI-lesions (by "voxel-based lesion symptom mapping") in oder to test the tumour-location-specific sensitivity and specificity of the different test included in the battery.

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Brief Summary in Scientific Language

Brain tumours are often associated with neurocognitive deficits. However, neurocognitive functioning is still widely neglected in neurooncology as a crucial brain function for treatment response as compared to language and motor functions. Recent studies provided evidence for the impact of neurocognitive deficits on health-related quality of life (Herman et al., 2003; Meyers et al., 2003; Giovagnoli et al., 2005). Moreover, neurocognitive function can serve as a strong independent predictor for overall survival as well as progression-free survival (Daniels et al., 2011). Neurocognitive decline may even be regarded as a sensitive tool for early detection of tumour progression, prior to radiological signs (Meyers et al., 2003; Brown et al., 2006). Regarding the effects of tumour treatment on neurocognitive functions, several drugs such as Bevacizumab have been accused to deteriorate neurocognitive functions (Taphoorn et al., 2004; Friedman et al., 2009; Wefel et al., 2011; Henriksson et al., 2011). However, a consensus regarding a practicable neurocognitive test battery for brain tumour patients is missing so far and the lack of standardized neurocognitive testing is a major deficit in most clinical trials. Moreover, location-specific test batteries are needed to allow efficient testing, especially regarding individual follow-up.
We, therefore, conduct a prospective evaluation of a novel test battery, which covers all crucial neurocognitive functions and requires 45 min testing time. The battery consists of validated and reliable tests based on the literature and empirical validation in our multidisciplinary research group. Some tests underwent partial shortening or simplification (to avoid tiring of the tumour patients and keep the efforts to a reasonable / feasible level). The battery includes the following tests: Digit Span Test (DST), Symbol Digit Modality Test (SDMT), Hopkins Verbal Learning Test – Revised (HVLT-R), Stroop Colour Word Test, Trail Making Test (TMT) A & B, Judgement of Line Orientation Test (JLOT), 9 Hole Pegboard Test, Controlled Oral Word Association Test (COWAT), Bells Test, Rey-Osterrieth Complex Figure Test (ROCFT), Mini Mental State Test (MMST) (table 1).
According to an a-priori power analysis, 192 patients with newly diagnosed monolocular, supratentorial contrast-enhancing intraaxial tumours (suspected glioblastoma) shall be allocated to the trial (N=128: tumor resection; N=64: stereotactic biopsy). To allow for faster recruitment, we chose a multicentric study approach. 12 university / teaching hospitals have provided written agreement to participate in the study.
The inclusion / follow-up in the study is independent from postoperative tumour treatment. The vast majority of patients is expected to receive and accomplish radiochemotherapy with concomitant Temozolomide (TMZ) (standard treatment; best medical care) within 8-10 weeks after discharge followed by adjuvant TMZ therapy. During the patients' regular stay in the hospital (for tumour surgery), neurocognitive testing will take place once before and twice on consecutive days (day 3-7) after surgery. Moreover, follow-up testing is planned at the time of the regular outpatients visits 3 months after surgery (+/- 4 weeks). This design enables conclusions regarding the effect of surgery (as compared to biopsy) and concomitant radiochemotherapy (3-months-follow-up) on neurocognitive functioning as well as to measure the retest reliability of the battery.

Another main objective of the study is to investigate correlations between MRI and psychometric test data. Therefore, the neuroimaging method 'voxel-based lesion symptom mapping' (VLSM; Bates et al., Nature Neuroscience, 2003) will be translated from basic neuroscience and stroke studies to neurooncology. The method allows a voxel-wise calculation of test statistics regarding the association of psychometric data such as test scores and the presence of lesion (here: tumour) within a given voxel. The respective values are rendered onto the brain surface to create a tumour-location-specific visualization of probable neurocognitive deficits. Those tests that show highly sensitivity and specificity for a specific tumour location can be used to establish shorter, location-specific test batteries.

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Organizational Data

  •   DRKS00010162
  •   2016/03/24
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  •   yes
  •   Approved
  •   14-109, Ethik-Kommission der Medizinischen Fakultät der Universität zu Köln
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Secondary IDs

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Health Condition or Problem studied

  •   C71.9 -  Malignant neoplasm: Brain, unspecified
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Interventions/Observational Groups

  •   Microsurgical tumour resection (with surgical aim of complete removal of CE-lesion) (N=128; incl. arm 3).
    The participation in the study does not influence the tumour treatment at all. In addition to the regular treatment and diagnostics, neurocognitive testing is performed (paper-based tests) at several times: During the patients' regular stay in the hospital (for tumour surgery), neurocognitive testing will take place once before and twice on consecutive days (day 3-7) after surgery. Moreover, follow-up testing is planned once at the time of the regular outpatients visits 3 months after surgery (+/- 4 weeks).
  •   Stereotactic Biopsy without relevant reduction of CE-lesion (< 10%) with surgical means (Arm 2: N=64)
  •   Stereotactic Biopsy followed by microsurgical tumour resection (with surgical aim of complete removal of CE-lesion)
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Other
  •   Other
  •   N/A
  •   N/A
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Primary Outcome

Alterations of neurocognitive functioning after brain tumour resection (vs. stereotactic biopsy). Herefore, changes of the individual test performance after surgery as compared to before surgery are assessed as changes in the test score values in % (individual level). Assessment at time points 1 vs. 3 (before surgery vs. after surgery = before discharge).

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Secondary Outcome

1. Alterations of neurocognitive functioning following radiochemotherapy (individual level in %; see primary endpoint) - Assessment at visits 3 & 4.
2. Test-retest-reliability of neurocognitive function assessment in glioblastoma patients (individual level; score values of each test; intraclass correlation coefficient) - Assessment at visits 2 & 3.
3. Correlation of neurocognitive deficits with tumour / oedema location (T-Scores of each test; voxel-based lesion symptom mapping) - Assessment at visits 1, 3 & 4.
4. Quality of life (SF-12 Score value) - Assessment at visits 1 & 4.
5. Depression (BDI Score value) - Assessment at visits 1 & 4.

Visite: (1) before surgery, (2/3) after surgery / before discharge, (4) +/- 3 months after surgery

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

  •   Planned
  •   2016/04/11
  •   192
  •   Multicenter trial
  •   National
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Inclusion Criteria

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

- contrast-enhancing cerebral tumor (suspection: glioblastoma): first diagnosed, supratentorial, unilateral, single lesion (no further intracerebral tumors)
- age > 18 yrs
- written informed consent
- good clinical state (KPS 70 or better, i.e., independent in basic daily life)

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Exclusion Criteria

- infratentorial, multiple or bihemispheric cerebral tumors (according to CE-T1), gliomatosis cerebri
- previous brain radiation therapy
- chemotherapy within 2 yrs prior to inclusion
- non-controlled epilepsy (despite anticonvulsive drugs > 3 focal seizures per day or > 1 generalized seizure within 3 days prior to 1st neurocognitive testing).
- abuse of drugs which may alter neurocognitive functioning (incl. alcohol) other than regular pain killers or regular anticonvulsive treatment < 24 hrs. prior to neurocognitive assessment.
- severe (chronic) migraine, cluster- or other headache
- severe depression (BDI Score > 30 / 63 pts or acute/decompensated psychiatric disorder)
- severe dementia (Mini Mental State Test [MMST] < 20 / 30 pts.)
- institutionalised patients
- contraindications regarding exposition to magnetic fields (MRI scan), e.g. metallic devices

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Addresses

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    • Uniklinik Köln, Zentrum für Neurochirurgie
    • 50937  Köln
    • Germany
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    • Uniklinik Köln, Allgemeine Neurochirurgie
    • Ms.  Dr.  Carolin  Weiß Lucas 
    • Kerpener Str. 62
    • 50937  Köln
    • Germany
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    • Uniklinik Köln, Allgemeine Neurochirurgie
    • Kay  Hölmer 
    • Kerpener Str. 62 / Haus 12
    • 50937  Köln
    • Germany
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Sources of Monetary or Material Support

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    • Uniklinik Köln, Allgemeine Neurochirurgie
    • Kerpener Str. 62
    • 50937  Köln
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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