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

• ClinicalTrials.gov Identifier: NCT02443948
• Recruitment Status: Unknown
• First Posted: May 14, 2015
• Last Update Posted: February 14, 2017
• Sponsor: Fondazione del Piemonte per l'Oncologia
• Information provided by (Responsible Party): Fondazione del Piemonte per l'Oncologia

Tracking Information

• First Submitted Date: March 19, 2015
• First Posted Date: May 14, 2015
• Last Update Posted Date: February 14, 2017
• Study Start Date: June 2014
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 11, 2015)

Correlation of change in cf-DNA levels with disease status in GIST patients harboring specific DNA mutations [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 11, 2015)

• Clearance of cf-DNA levels after surgery in GIST patients harboring specific DNA mutations [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Cf-DNA blood samples will be collected in EDTA tubes during the routine blood test.

• 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.
• Condition: Gastrointestinal Stromal Tumor (GIST)

Intervention

Other: Vena puncture for blood collection

Cf-DNA blood samples will be collected in EDTA tubes (20 ml) during the routine blood test

Study Groups/Cohorts

• adjuvant/follow up setting
  Intervention: Other: Vena puncture for blood collection
• neo-adjuvant setting
  Intervention: Other: Vena puncture for blood collection
• advanced disease
  Intervention: Other: Vena puncture for blood collection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 11, 2015): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2018
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT02443948
• Other Study ID Numbers: cf-DNA GIST
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fondazione del Piemonte per l'Oncologia
• Original Responsible Party: Same as current
• Current Study Sponsor: Fondazione del Piemonte per l'Oncologia
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fondazione del Piemonte per l'Oncologia
• Verification Date: February 2017