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

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

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.

Study Overview

• Status: Unknown
• Conditions: Gastrointestinal Stromal Tumor (GIST)
• Intervention / Treatment: Other: Vena puncture for blood collection

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.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Italy
  • TO
    • Candiolo, TO, Italy, 10060
      • Recruiting
      • Fondazione del Piemonte per l'Oncologia
      • Contact: Giovanni Grignani, MD; Phone Number: 3623 +39011993; Email: giovanni.grignani@ircc.it
      • Contact: Alberto Bardelli, Prof.; Phone Number: 3235 +39.011.993; Email: alberto.bardelli@ircc.it
      • Sub-Investigator: Sandra Aliberti, MD
      • Sub-Investigator: Erica Palesandro, MD
      • Sub-Investigator: Paola Boccone, MD
      • Sub-Investigator: Danilo Galizia, MD
      • Sub-Investigator: Sara Miano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione del Piemonte per l'Oncologia

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2017
• Study Completion (ANTICIPATED): June 1, 2018

Study Registration Dates

• First Submitted: March 19, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (ESTIMATE): May 14, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: cf-DNA GIST