Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00009673

Trial Description

start of 1:1-Block title

Title

Clinical Value of [18]Fluoroethylcholine Positron-Emission-Tomography Combined With Endorectal Magnetic Resonance Imaging by Software Fusion for Pre-therapeutic Staging of Prostate Cancer

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

FEC-PET/MRI

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

To investigate the sensitivity of the [18F]fluoroethylcholine (FEC)
Positron-Emission-Tomography/ Magnetic Resonance Imaging (PET/MRI) method in tumour
detection and location (side assignment, encapsulation, invasion of the seminal vesicle) and
detection of affected lymph nodes, and to compare these with presently used detection
procedures (needle biopsy, digital rectal examination, transrectal ultrasound, and
pre-therapeutic assessment), with a view to finding out whether the [18F]fluoroethylcholine
PET/MRI method is comparable to, or superior to, the established method. Postoperative
histology served as the standard of reference.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Prostate carcinoma is today in Germany the most frequently diagnosed cancer disease of men
and is - after bronchial carcinoma - their second most frequent cause of cancer-related
death. Around 22% of all new cancer diagnoses among males are prostate-related. This
corresponds to an age-adjusted incidence rate of nearly 100 per 100,000 males in the
population, and to well above 40,000 new diagnoses of prostate cancer per year
[Robert-Koch-Institut, 2010]. The dramatic increase in recent decades is attributable more
to improved diagnostic methods and a generally increased life expectancy than to an actual
increase in the incidence of disease [Robert-Koch-Institut, 2010].

The total annual mortality rate is around 11,000 [Statistisches Bundesamt, 1994]. Prostate
carcinoma is virtually unknown among men under 40 years of age. The annual prevalence rises
with increasing age - between the 40th and 80th years of life by a factor of more than 1000.
Autopsies have shown that among men over 70 up to 80% have a latent prostate carcinoma,
without it being fatal [Breslow 1977; Börgemann, 2006]. The patients' average age at
diagnosis is 71 years.

The five-year prostate-cancer-specific survival rate after diagnosis is about 80-99% for
tumours that are restricted to the gland itself [Porter, 2006]. For disseminated tumours
this figure is considerably smaller, not more than 35% [von Eschenbach, 1996]. A prospect of
complete regression exists only for non-metastasing carcinomas, but there it is quite good:
under aggressive treatment, 90% of cancers restricted to the prostate itself can be
completely cured, as can 50% of those that have crossed the gland's capsule [Deutsche
Gesellschaft für Urologie, 2009].

At present, there is a lack of adequate pre-therapeutic staging methods. This in turn often
prevents the reliable choice of a stage-adapted therapeutic regimen, which could possibly
offer a better prognosis even for carcinomas extending into neighbouring organs. A
consequence of this uncertainty is that in individual cases the therapy is not ideally
suited to the stage of disease, and the success of radiation treatment, hormonal therapy and
chemotherapy can only approximately be matched with the stage of dissemination. Until now,
the only reliable method for lymph-node diagnosis is operative staging by lymphadenectomy.
No reliable diagnostic method is available by which the degree of spreading of the tumour
within the prostate can be established.

In this context, Positron-Emission-Tomography (PET) examination with radioactively labelled
choline appears to offer a promising primary imaging-diagnostic staging method, as indicated
by the studies reviewed below. This diagnostic method as applied to humans was first
described by Gauthier et al. [1985]. This was followed by two detailed reports from a
Japanese group: Hara et al. [1997] first investigated the potential of [11C]choline in brain
tumours and found a clear enrichment of this marker in the tumours of 24 patients, while
normal brain tissue was not enriched with it. In a subsequent study by the same group [Hara,
1998], the enrichment of fluorodeoxyglucose was compared with the choline uptake in the
lesions of ten prostate-cancer patients. Thus, the choline enrichment (SUV, standardised
uptake value) was 3.48 ± 1.31 in 43 lesions, while in the normal environment of the lesser
pelvis the corresponding value was below 1.0. De Jong et al. [2003] investigated 67
patients, of whom 15 had histologically confirmed lymph-node metastases: the [11C]choline
test gave a 'true positive' result in 12 of 15 patients and a 'false negative' in 3
patients, thus indicating that [11C]choline PET is sufficiently sensitive and specific for
the pre-operative staging of lymph-node metastases of prostate carcinoma. In a pre-operative
staging using Magnetic Resonance Imaging (MRI) with a combined endorectal and
body-phased-array coil, Pegios et al. [2003] investigated 42 patients with strong clinical
suspicion, or with needle-biopsy confirmation, of prostate cancer and were able to
differentiate between stages of extracapsular growth and seminal-vesicle infiltration (tumor
stage T2 versus T3 [T2=tumor restricted to the gland itself; T3a=extracapsule growing of the
tumor; T3b= tumor infiltration into the seminal-vesicles]) with an accuracy of 94-97%
(sensitivity 100%, specificity between 87% and 93% for observers 1 and 2). The exact, local
tumour stage was identified with an accuracy of 75%. However, for lymph-node infiltration a
sensitivity of only 25% was achieved: one of four lymph-node-positive patients was correctly
identified. In a more recent study, a Japanese group [Yamaguchi, 2005] investigated the
application of nuclear magnetic resonance (NMR) spectroscopy, magnetic resonance imaging
(MRI) and choline-PET in 20 patients with needle-biopsy-confirmed prostate cancer. The PET
imaging achieved a sensitivity of 100%, NMR (quotient [(creatine + choline) / citrate]) 65%
and unsupported MRI 60%. For 16 patients radical prostatectomy was performed; results
correlated with those of pre-operative local staging with PET by 81%, and with MRI by 50%.
The site of choline uptakes in PET was visualised by MRI using the distance of the prostate
from the femoral head and the pubic symphysis.At present, no data relevant for the present
study indication are available on the software-fused imaging by combined PET/MRI. The
combination of high-resolution endorectal MRI with functional PET imaging could come to
offer a decisive advantage in the staging of prostate carcinoma. The present study was
designed to test this in an appropriate patient population.

A system combining PET and MRI was recently granted approval in the U.S.A. by the U.S. Food
and Drug Administration [FDA, 2011].

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00009673
  •   2015/11/11
  •   2007/08/23
  •   yes
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2006-003933-33 
  •   NCT00520546  (ClinicalTrials.gov)
  •   12K3-S-140708  (Dr. Markus Hartenbach)
  •   2006-003933-33 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Prostate Cancer
  •   C61 -  Malignant neoplasm of prostate
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Other: 18F-Ethylcholine Positron Emission Tomography (FEC-PET)
  •   Other: Endorectal Magnetic Resonance Imaging (1.5Tesla) (eMRI)
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Diagnostic
  •   Single (group)
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- Number of Participants With Positive or Negative Results in PET, MRI or PET/MRI for Prostate Cancer Compared to Histological Findings; time frame: within < 2 weeks after PET/MRI; PET positive lesions were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. At least 1 histological confirmed cancer lesion has to be detected by each of the 3 methods to be patient based true positive.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in All Patients; time frame: within < 2 weeks after PET/MRI; PET positive lesions (n=128) were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative and positive predictive values were determined.
- Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Gleason Score >6 (3+3); time frame: within < 2 weeks after PET/MRI; PET positive lesions in patients with Gleason >6(3+3),n=43 were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative & positive predictive values were determined.
- Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Malignant Lesions >5mm (n=98); time frame: within < 2 weeks after PET/MRI; PET positive lesions were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative and positive predictive values were determined without malign lesions <=5mm.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2007/12/31
  •   44
  •   [---]*
  •   [---]*
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Male
  •   50   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- Histologically diagnosed prostate cancer (needle biopsy)

- Radical prostatectomy as primary treatment

- No nutrition within 12 hours before Positron-Emission-Tomography (PET)

- No food containing choline within 24 hous before PET

- Age > 50 years

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

- Total endo-prothesis of the hip region

- Clinical or chemical detection of an acute infection

- Missing patient agreement

- Secondary cancer

- Surgical treatment within 3 month before PET

- Claustrophobia

- Medical drugs with choline

- Severe liver damage

- Cardiac infarction

- Bradycardia (pulse rate < 55/min)

- Allergic reaction against Neurotropan

- Bronchial asthma

- Cardiac pacemaker

- Small metal implants (e.g., clips, cochlea-implants, etc.)

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Dr. Markus Hartenbach
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • German Federal Armed Forces Hospital, Ulm, Dep. of Nuclear Medicine
    • Markus Hartenbach, Dr. 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • German Federal Armed Forces Hospital, Ulm, Dep. of Nuclear Medicine
    • Markus Hartenbach, Dr. 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up complete
  •   2011/06/01
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  •   Robert-Koch-Institut (2010): Krebs in Deutschland 2005/2006 Häufigkeiten und Trends. A collaborative publication of the Robert-Koch-Institut and the Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. [Society for epidemiological cancer register], 7th edition, Berlin.
  •   Börgermann C, Rübben H (2006): Früherkennung des Prostatakarzinoms [Early recognition of prostate carcinoma]. Dtsch Arztebl. 103: 2399-2406.
  •   Breslow N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H. Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France. Int J Cancer. 1977 Nov 15;20(5):680-8.; 924691
  •   de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J Nucl Med. 2003 Mar;44(3):331-5.; 12620996
  •   Deutsche Gesellschaft für Urologie (2009): Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms [Interdisciplinary guideline for the early recognition, diagnosis and therapy of the various stages of prostate carcinoma]. Deutsche Gesellschaft für Urologie e. V. (ed.), p. 53 ff.
  •   FDA (2011): FDA clears new system to perform simultaneous PET, MRI scans. Available on-line at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2011/ucm258700.htm
  •   Gauthier S, Diksic M, Yamamoto L, Tyler J, Feindel WH (1985): Positron emission tomography with [11C]-choline in human subjects. Can J Neurol Sci 12: 214.
  •   Hara T, Kosaka N, Shinoura N, Kondo T. PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med. 1997 Jun;38(6):842-7.; 9189127
  •   Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med. 1998 Jun;39(6):990-5.; 9627331
  •   Hara T, Kosaka N, Kishi H. Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med. 2002 Feb;43(2):187-99.; 11850483
  •   Kwee SA, Coel MN, Lim J, Ko JP. Prostate cancer localization with 18fluorine fluorocholine positron emission tomography. J Urol. 2005 Jan;173(1):252-5.; 15592091
  •   Pegios W, Bentas W, Wittmann L, Mack MG, Zangos S, Söllner O, Binder J, Fellbaum C, Jonas D, Vogl TJ. [MRI staging of prostate cancer with the combined endorectal body phased-array coil and histologic correlation]. Rofo. 2003 Dec;175(12):1660-6. German.; 14661137
  •   Porter CR, Kodama K, Gibbons RP, Correa R Jr, Chun FK, Perrotte P, Karakiewicz PI. 25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series. J Urol. 2006 Aug;176(2):569-74.; 16813891
  •   Yamaguchi T, Lee J, Uemura H, Sasaki T, Takahashi N, Oka T, Shizukuishi K, Endou H, Kubota Y, Inoue T. Prostate cancer: a comparative study of 11C-choline PET and MR imaging combined with proton MR spectroscopy. Eur J Nucl Med Mol Imaging. 2005 Jul;32(7):742-8. Epub 2005 Mar 15.; 16052370
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2016/01/14


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