Circulating Cell-free Tumor DNA in the Plasma of Patients With Gastrointestinal Stromal Tumors (GIST)

Study Overview
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Brief Summary
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This observational study is proposed to evaluate if the trend in the levels of cf-DNA evaluated on a sample of peripheral blood may be related to different clinical behaviors of the disease monitored by radiological investigations conducted.

Detailed Description
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Demetri and colleagues presented, at the AACR and ASCO Annual Meeting 2013, an exploratory analysis to assess GIST genotypes on patients in the GRID study. Mutations in the KIT gene were detected in 58 percent of the blood samples compared with 66 percent of the tumor tissue samples (31). However, when focusing their analysis on secondary KIT mutations, which are the mutations that drive resistance to targeted therapies like imatinib and sunitinib, the researchers found mutations in 47 percent of blood samples compared with only 12 percent of tissue samples. In addition, nearly half of blood samples in which secondary KIT mutations were found, harbored multiple secondary mutations. Therefore, cf-DNA may become an efficient marker of mutational GIST status and disease itself. On this basis, this trial aims to evaluate whether tumor DNA carrying mutations (for KIT, PDGFRα, BRAF, RAS, SDH) can be detected and quantified in the plasma of patients with GISTs, either with active disease or during follow-up, and whether detection can be correlated with the disease status.

Official Title
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Circulating Cell-free Tumor DNA in the Plasma of Patients With Gastrointestinal Stromal Tumors (GIST): Detection and Correlation With Disease Status Assessed by Conventional Technique. Prospective Observational Study

Conditions
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Gastrointestinal Stromal Tumor (GIST)

Intervention / Treatment
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* Other: Vena puncture for blood collection


Participation Criteria
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Eligibility Criteria
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Male or female patients aged >= 18 years Histologically confirmed diagnosis of GIST of any anatomical location either by biopsy or surgical specimen Available archival tumor tissue Signed informed consent form Exclusion Criteria: Impossibility to ensure adequate clinical and serum sample follow-up Serious psychiatric disease that precludes informed consent or limits compliance

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| adjuvant/follow up setting<br> | Other: Vena puncture for blood collection<br>* Cf-DNA blood samples will be collected in EDTA tubes (20 ml) during the routine blood test<br>|
| neo-adjuvant setting<br> | Other: Vena puncture for blood collection<br>* Cf-DNA blood samples will be collected in EDTA tubes (20 ml) during the routine blood test<br>|
| advanced disease<br> | Other: Vena puncture for blood collection<br>* Cf-DNA blood samples will be collected in EDTA tubes (20 ml) during the routine blood test<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of change in cf-DNA levels with disease status in GIST patients harboring specific DNA mutations | To assess the correlation of change in cf-DNA levels with disease status evaluated according to RECIST criteria v 1.1 | baseline, every 12 weeks, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of cf-DNA levels after surgery in GIST patients harboring specific DNA mutations | To evaluate the time (half-life esteem) of cf-DNA levels clearance after definitive surgery | the day before surgery, every 12 weeks, up to 2 years | 
| Detection of secondary mutations in KIT, PDGFRα and/or other genes | To evaluate the possibility to detect secondary mutations in KIT, PDGFRα and/or other genes | baseline, every 12 weeks, up to 2 years | 
| Correlation of cf-DNA levels with overall survival (OS) | To evaluate the correlation between cf-DNA levels and overall survival (time from the date of enrollment to date of death or to the date being censored at two years, whichever occurs first) | baseline and up to 2 years | 
| Correlation of detection of secondary mutations in KIT, PDGFRα and/or other genes with radiological disease progression | To correlate the detection of secondary mutations in KIT, PDGFRα and/or other genes with radiological disease progression according to RECIST criteria v 1.1 | baseline, every 12 weeks, up to 2 years | 
| Correlation of the level of cf-DNA related to disease status in GIST patients harboring specific DNA mutations | To assess if the cf-DNA levels are related to disease status detected according to Choi criteria. | baseline, every 12 weeks, up to 2 years |