Clinical trial NCT02443948: Circulating Cell-free Tumor DNA in the Plasma of Patients With Gastrointestinal Stromal Tumors (GIST)
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Gastrointestinal Stromal Tumor (GIST)
Lead sponsor: Fondazione del Piemonte per l'Oncologia
Sponsor class: OTHER
First posted: 2015-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population includes adult patients with histologically confirmed GIST, either with active disease or in follow-up.

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.

Eligibility 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

Primary outcomes:
measure: Correlation of change in cf-DNA levels with disease status in GIST patients harboring specific DNA mutations
timeFrame: baseline, every 12 weeks, up to 2 years
Secondary outcomes:
measure: Clearance of cf-DNA levels after surgery in GIST patients harboring specific DNA mutations
timeFrame: the day before surgery, every 12 weeks, up to 2 years
measure: Detection of secondary mutations in KIT, PDGFRα and/or other genes
timeFrame: baseline, every 12 weeks, up to 2 years
measure: Correlation of cf-DNA levels with overall survival (OS)
timeFrame: baseline and up to 2 years
measure: Correlation of detection of secondary mutations in KIT, PDGFRα and/or other genes with radiological disease progression
timeFrame: baseline, every 12 weeks, up to 2 years
measure: Correlation of the level of cf-DNA related to disease status in GIST patients harboring specific DNA mutations
timeFrame: baseline, every 12 weeks, up to 2 years
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia
state: TO
Study officials:
References: