Trial document




drksid header

  DRKS00008173

Trial Description

start of 1:1-Block title

Title

Optimized Response Assessment of Gastrointestinal Stromal Tumors Using Dual-Energy CT: A Prospective Multicenter-Multinational Trail in Patients Undergoing Targeted Therapy with a tyrosine-kinase-inhibitor

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

Trial Acronym

[---]*

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

Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma tumors of the gastrointestinal tract that start in special cells in the wall of the gastrointestinal tract. The traditional therapy approach is surgical removal and chemotherapy. New, targeted therapies use tyrosine kinase inhibitors (TKI) for specific treatment of GIST, inhibiting tumor proliferation. Follow up assessment of tumor response under therapy is mandatory in order to detect early non-responders. GIST, which are treated with TKI almost always show different response patterns than tumors treated with cytotoxic chemotherapy. Tumor manifestations treated with targeted therapies often show only minor measurable changes in tumor size despite inhibition of tumor proliferation. Decrease in tumor size fulfilling the criteria of a partial remission according to Response Evaluation Criteria In Solid Tumors (RECIST) may occur at a delayed therapy stage (e.g. several months). Sometimes, even an initial increase of maximum tumor diameter may be observed, despite the fact that those patients are treatment responders with respect to ‘hard’ study endpoints like overall survival or progression free survival.
This results in a misclassification of patients as non-responders in an early therapy stage. As a consequence, effective treatment is either missed or decisions towards a less effective second-line therapy are made.
To overcome this issue, alternative response criteria have been proposed for GIST (i.e. Choi criteria). In addition to conventional size measurements, Choi criteria consider tumor density changes based on simple CT density measurements. Although this approach is certinly a correct step towards a more individualized tumor response assessment the major limitation of the Choi criteria is that tumor density changes are also influenced by other independent factors like tumor hemorrhage or calcification during TKI-therapy. Thus, direct quantification of tumor blood flow as a surrogate of tumor viability will likely be more accurate and robust than simple tumor density measurements.
Dual Energy CT (DECT) is a new and robust CT method that allows to exactly quantify the intra-tumoral amount of intravenously injected iodinated contrast material and therefore indirect lesion blood flow to a certain time point. In this study 100 patients with proven GIST undergoing TKI treatment will be enrolled. The study period will be 60 months, including 2 years of patient recruitment and 3 years of follow-up after the last recruitment. Each patient will receive a clinically indicated biphasic DECT scan of the abdomen before starting treatment or before a change in therapy is indicated. Further each patient will undergo the same biphasic DECT protocol for follow-up assessment.
The hypothesis of this prospective multi-center study is that DECT is more accurate for the evaluation of immediate therapeutic response in patients with GIST who undergo TKI inhibitor therapy than conventional methods.

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

Brief Summary in Scientific Language

Patients with Gastrointestinal stromal tumors (GIST) which are treated with targeted therapies by tyrosine kinase inhibition (TKI) almost always show different response patterns than tumors treated with cytotoxic chemotherapy. Tumor manifestations treated with targeted therapies often show only minor measurable changes in tumor size despite inhibition of tumor proliferation. Decrease in tumor size fulfilling the criteria of a partial remission according to Response Evaluation Criteria In Solid Tumors (RECIST) may occur at a delayed therapy stage (e.g. several months). Sometimes, even an initial increase of maximum tumor diameter may be observed, despite the fact that those patients are treatment responders with respect to ‘hard’ study endpoints like overall survival or progression free survival.
This results in a misclassification of patients as non-responders in an early therapy stage. As a consequence, effective treatment is either missed or decisions towards a less effective second-line therapy are made.
To overcome this issue, alternative response criteria have been proposed for GIST (i.e. Choi criteria). In addition to conventional size measurements, Choi criteria consider tumor density changes based on simple CT density measurements. Although this approach is certainly a correct step towards a more individualized tumor response assessment the major limitation of the Choi criteria is that tumor density changes are also influenced by other independent factors like tumor hemorrhage or calcification during TKI-therapy. Thus, direct quantification of tumor perfusion as a surrogate of tumor viability will likely be more accurate and robust than simple tumor density measurements.
Dual Energy CT (DECT) is a new and robust CT method that allows to exactly quantify the intra-tumoral amount of intravenously injected iodinated contrast material. Thus, the technique can be considered as a simple and reliable surrogate of snap-shot tumor perfusion.
In this study 100 patients with proven GIST undergoing TKI treatment will be enrolled. The study period will be 60 months, including 2 years of patient recruitment and 3 years of follow-up after the last recruitment. Each patient will receive a clinically indicated biphasic DECT scan of the abdomen before starting treatment or before a change in therapy is indicated. Further each patient will undergo the same biphasic DECT protocol for follow-up assessment.
The hypothesis of this prospective multi-center study is that DECT is more accurate for the evaluation of immediate therapeutic response in patients with GIST who undergo TKI inhibitor therapy than conventional methods.

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

Organizational Data

  •   DRKS00008173
  •   2015/07/29
  •   [---]*
  •   yes
  •   Approved
  •   2013-628N-MA, Medizinische Ethik-Kommission II Medizinische Fakultät Mannheim der Universität Heidelberg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1171-6041 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C16 -  Malignant neoplasm of stomach
  •   C17 -  Malignant neoplasm of small intestine
  •   C18 -  Malignant neoplasm of colon
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Patients with Gastrointestinal Stromal Tumors undergoing tyrosine kinase inhibitor treatment will be assessed regarding progression-free survival and overall survival within 3 years using the standard response criteria, in particular Response Evaluation Criteria In Solid Tumors, the WHO criteria for response, the tumor lesion volume as well as tumor density (according to Choi).
  •   Patients with Gastrointestinal Stromal Tumors undergoing tyrosine kinase inhibitor treatment will be assessed regarding progression-free survival and overall survival within 3 years using the response criteria, in particular tumor lesion iodine uptake normalised to the aorta and tumor lesion iodine uptake normalised to the portal vein.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   No
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Progression-free survival within 3 years.

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

Secondary Outcome

Overall survival within 6 years.

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

Countries of Recruitment

  •   Germany
  •   Italy
  •   United Kingdom
  •   Japan
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2015/08/03
  •   100
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

All patients being diagnosed with Gastrointestinal Stromal Tumors and undergoing tyrosine kinase inhibitor treatment will be included.

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

Exclusion Criteria

Patients younger than 18 years or with contraindication to a contrast-enhanced CT scan.

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

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Mannheim
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    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
    • Universitätsklinikum Mannheim
    • Mr.  Dr.  Mathias  Meyer 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    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
    • Universitätsklinikum Mannheim
    • Ms.  Silke  Bittorf 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    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
    • Siemens Healthcare GmbH
    • Siemensstr. 1
    • 91301  Forchheim
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
  • start of 1:1-Block address otherSupport
    • Universitätsklinikum Mannheim
    • Mr.  Priv.-Doz. Dr.  Thomas  Henzler 
    • Theodor-Kurzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address otherSupport
    start of 1:1-Block address contact otherSupport
    end of 1:1-Block address contact otherSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.