Clinical trial NCT02595645: GENESIS: Genetic Biopsy for Prediction of Surveillance Intervals After Endoscopic Resection of Colonic Polyps
Official title: GENESIS: Genetic Biopsy for Prediction of Surveillance Intervals After Endoscopic Resection of Colonic Polyps
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colonic Polyps
Keywords: colorectal adenoma
colorectal cancer
next generation sequencing
liquid biopsy
screening colonoscopy
surveillance strategies
Lead sponsor: University of Ulm
Sponsor class: OTHER
Collaborators: name: Technical University of Munich
name: Medical University of Graz
name: Specialized Medical Office for Gastroenterology Dornstadt
name: QIAGEN Gaithersburg, Inc
First posted: 2015-11-03
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: Colorectal cancer ist the 2nd most leading cancer among men and women in germany. Screening colonoscopy has the potential to detect premalignant lesions. By endoscopical resection of these lesions, colorectal cancers could be avoided. The decision for surveillance is made according to patients medical history, amount and histological characteristics of the resected polyps. Molecular guided decisions are still missing. Thus, further tools and mechanisms, beyond but in addition to endoscopy and histopathological, are strongly required to reduce such interval carcinomas and get a better and deeper inside into molecular alterations which occurs in premalignant lesions in the colon and describe risk populations which might benefit from shorter surveillance strategies by colonoscopy. Therefore GENESIS will enroll 100 patients, which underwent screening colonoscopy with polyp ectomy. All biopsies were stored and processed without formalin in special boxes (PaxGene by Qiagen®). After microdissection of polyp tissue and isolation of DNA targeted next generation sequencing of 38 cancer-related genes followed by bioinformatics and systems biology analyses. The sequencing results were correlated to the endoscopical and histopathological findings. In parallel we are collecting EDTA-blood samples for analysis of circulating cell-free DNA (cfDNA) to investigate the potential of liquid biopsies in premalignant colorectal lesions.

Detailed description: Colorectal cancer ist the 2nd most leading cancer among men and women in germany. Screening colonoscopy is provided for all people over 55 years in germany to detect and remove precancerous lesions (polyps) and thereby prevent the occurence of colorectal cancers. According to the result of screening colonoscopy and histopathological examination of the removed polyps the next examination will be planned. But so called interval carcinomas were observed with increasing incidence. Thus, further tools and mechanisms, beyond but in addition to endoscopy and histopathology, are strongly required to reduce such interval carcinomas and get a better and deeper inside into molecular alterations which occurs in premalignant lesions in the colon and describe risk populations which might benefit from shorter surveillance strategies by colonoscopy. Therefore we will enroll 100 patients, which underwent screening colonoscopy with polyp ectomy. Each polyp, provided for endoscopical removal, well be biopsied and stored separately. In each case, diagnosis is ensured. Per patient a maximum of 6 biopsies (from 6 different polyps) is intended. All biopsies were stored and processed without formalin in special boxes (PaxGene by Qiagen®). After microdissection of polyp tissue and isolation of DNA targeted next generation sequencing of 38 genes (ACVR1B, DCC, MIER3, SLC9A9, AKT1, DMD, MLH1, SMAD2, APC, EP300, MSH2, SMAD4, ATM, ERBB2, MSH3, TCERG1, ATP6V0D2, FBXW7, MSH6, TCF7L2, BAX, FZD3, MYO1B, TGFBR2, BRAF, GPC6, NRAS, TP53, CASP8, KRAS, PIK3CA, WBSCR17, CDC27, MAP2K4, PIK3R1, CTNNB1, MAP7, PTPN12) followed by bioinformatics and systems biology analyses. The sequencing results were correlated to the endoscopical and histopathological findings. In parallel we are collecting EDTA-blood samples for analysis of circulating cell-free DNA (cfDNA). NGS targeted sequencing of these 38 genes should also be performed on cfDNA level to investigate the potential of liquid biopsies in premalignant colorectal lesions.

Eligibility criteria: Inclusion Criteria:

* written informed consent
* indication of screening colonoscopy

Exclusion Criteria:

* chronic inflammatory bowl disease
* known colorectal cancer (except curative treated colorectal cancers more than 5 years ago)
* disagreement in participation

Primary outcomes:
measure: Genetic landscape of colonic polyps based on NGS-analysis
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University Graz
state: Steiermark
city: Dornstadt
country: Germany
facility: Specialized Medical Office for Gastroenterology
state: Baden-Württemberg
city: Ulm
country: Germany
facility: University Ulm, Internal Medicine I, Interventional and Experimental Endoscopy (InExEn)
state: Baden-Württemberg
city: Munich
country: Germany
facility: Technical University Munich
state: Bavaria
Study officials:
affiliation: University Ulm, Internal Medicine I, Interventional and experimental endoscopy (InExEn)
name: Alexander G. Meining, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: