Gastrointestinal Stromal Tumor (GIST)
Conditions
Brief summary
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
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.
Interventions
Cf-DNA blood samples will be collected in EDTA tubes (20 ml) during the routine blood test
Sponsors
Fondazione del Piemonte per l'Oncologia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of change in cf-DNA levels with disease status in GIST patients harboring specific DNA mutations | baseline, every 12 weeks, up to 2 years | To assess the correlation of change in cf-DNA levels with disease status evaluated according to RECIST criteria v 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of cf-DNA levels after surgery in GIST patients harboring specific DNA mutations | the day before surgery, every 12 weeks, up to 2 years | To evaluate the time (half-life esteem) of cf-DNA levels clearance after definitive surgery |
| Detection of secondary mutations in KIT, PDGFRα and/or other genes | baseline, every 12 weeks, up to 2 years | To evaluate the possibility to detect secondary mutations in KIT, PDGFRα and/or other genes |
| Correlation of cf-DNA levels with overall survival (OS) | baseline and up to 2 years | 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) |
| Correlation of detection of secondary mutations in KIT, PDGFRα and/or other genes with radiological disease progression | baseline, every 12 weeks, up to 2 years | 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 |
| Correlation of the level of cf-DNA related to disease status in GIST patients harboring specific DNA mutations | baseline, every 12 weeks, up to 2 years | To assess if the cf-DNA levels are related to disease status detected according to Choi criteria. |
Countries
Italy
Outcome results
None listed