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

Study Description

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.

Condition or disease	Intervention/treatment
Gastrointestinal Stromal Tumor (GIST)	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 Design

• Study Type: Observational
• Estimated Enrollment: 60 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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 Start Date: June 2014
• Estimated Primary Completion Date: December 2017
• Estimated Study Completion Date: June 2018

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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)
4. 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
5. 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.

Biospecimen Retention:   Samples With DNA

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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

Contacts and Locations

Locations

Italy

Fondazione del Piemonte per l'Oncologia; Recruiting

Candiolo, TO, Italy, 10060

Contact: Giovanni Grignani, MD +39011993 ext 3623 giovanni.grignani@ircc.it

Contact: Alberto Bardelli, Prof. +39.011.993 ext 3235 alberto.bardelli@ircc.it

Sub-Investigator: Sandra Aliberti, MD

Sub-Investigator: Erica Palesandro, MD

Sub-Investigator: Lorenzo D'Ambrosio, MD

Sub-Investigator: Paola Boccone, MD

Sub-Investigator: Danilo Galizia, MD

Sub-Investigator: Sara Miano, MD

Sponsors and Collaborators

Fondazione del Piemonte per l'Oncologia

More Information

• Responsible Party: Fondazione del Piemonte per l'Oncologia
• ClinicalTrials.gov Identifier: NCT02443948
• Other Study ID Numbers: cf-DNA GIST
• First Posted: May 14, 2015
• Last Update Posted: February 14, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases