Volatile Markers in Digestive Cancer

NCT02332213 | Completed

• 2 other identifiers: 2914LZP Nr. 2014.10-5
• Study Type: observational
• Target: 2,022
• Locations: 2 countries
• Sites: 2

Brief Summary

The study is aimed to determine the potential of volatile marker testing for identification of gastrointestinal cancers (in particular - colorectal and gastric cancers), the related precancerous lesions in the stomach and colon. The study will be addressing the role of confounding factors, including lifestyle factors, diet, smoking as well as addressing the potential role of microbiota in the composition of exhaled volatile markers.

Conditions

Colorectal Cancer; Colorectal Adenoma; Gastric Cancer; Peptic Ulcer Disease; Atrophic Gastritis; Intestinal Metaplasia; H.Pylori Infection; Normal Control; Average-risk General Population

Keywords

Volatile organic compounds; Nanosensor technology; GC-MS; Breath-testing; Digestive cancer; Precancerous lesions; Colorectal cancer; Adenoma; Gastric cancer; Atrophic gastritis; OLGIM

Outcome Measures

Primary Outcomes (2)

• Performance of nanoarray sensor testing to detect target lesions

  Sensitivity, specificity, overall accuracy of nanoarray sensor testing for VOCs to detect the target lesions in the blinded analysis

  At the time of breath sampling

• VOCs differentiating the study groups

  List of VOCs assayed by GC-MS with statistical difference between the study groups

  At the time of breath sampling

Secondary Outcomes (3)

• Identification of characteristic VOC pattern in risk age groups

  At the time of sampling

• VOC pattern changes following treatment

  At baseline and every 6 months within 3 year period

• Groups of gastrointestinal microbiota correlating to VOCs

  At the time of sampling

Other Outcomes (3)

• VOC pattern changes following intervention to microbiota

  At baseline and following the intervention (1 week, 1 month)

• Gastric microbiome changes following intervention to microbiota

  At baseline and 3 years after intervention

• Gastrointestinal microbiome in cancer patients

  At the time of sampling

Study Arms (9)

1. Colorectal cancer

Patients with histologically confirmed colorectal cancer (adenocarcinoma)

Procedure: Breath sampling for volatile marker detection; Procedure: Colonoscopy with biopsies or lesion removal when required; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition; Procedure: Histological evaluation of the surgery material

2. Colorectal high-risk lesions

Patients without colorectal adenocarcinoma, but carrying high-risk adenomatous polyps being described by one of the following: 1) size≥1 cm; 2) high-grade dysplasia; 3) villous component. Prior to removal of the lesions.

Procedure: Breath sampling for volatile marker detection; Procedure: Colonoscopy with biopsies or lesion removal when required; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

3. Colorectal low-risk adenoma

Patients without colorectal adenocarcinoma and without colorectal high-risk lesions as described under Group 2 criteria

Procedure: Breath sampling for volatile marker detection; Procedure: Colonoscopy with biopsies or lesion removal when required; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

4. Group of control (colorectal)

Patients having undergone colonoscopy without an evidence for colorectal lesions fulfilling Group 1 or Group 2 or Group 3 criteria. Prior to removal of the lesions.

Procedure: Breath sampling for volatile marker detection; Procedure: Colonoscopy with biopsies or lesion removal when required; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

5. Gastric cancer

Patients with histologically confirmed gastric cancer (adenocarcinoma)

Procedure: Breath sampling for volatile marker detection; Procedure: Upper endoscopy with biopsies; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition; Procedure: Histological evaluation of the surgery material

6. Gastric dysplasia

Patients without gastric adenocarcinoma but with histologically confirmed dysplasia (either high- or low-grade) of the stomach

Procedure: Breath sampling for volatile marker detection; Procedure: Upper endoscopy with biopsies; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

7. High-risk gastric lesions

Patients graded Stage III-IV according to OLGIM (Operative Link of Gastric Intestinal Metaplasia Assessment) staging system, but excluding those with dysplasia (Group 5)

Procedure: Breath sampling for volatile marker detection; Procedure: Upper endoscopy with biopsies; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

8. Normal and low-risk gastric lesions

Staged 0-III according to OLGIM. Dysplasia should be excluded

Procedure: Breath sampling for volatile marker detection; Procedure: Upper endoscopy with biopsies; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

9. Average risk population

Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer.

Procedure: Breath sampling for volatile marker detection; Procedure: Plasma/serum sampling; Procedure: Faecal sample acquisition

Interventions

Breath sampling for volatile marker detection PROCEDURE

Acquisition of two exhaled breath samples of alveolar air to be analysed by GCMS and nanosensor technology

1. Colorectal cancer; 2. Colorectal high-risk lesions; 3. Colorectal low-risk adenoma; 4. Group of control (colorectal); 5. Gastric cancer; 6. Gastric dysplasia; 7. High-risk gastric lesions; 8. Normal and low-risk gastric lesions; 9. Average risk population

Upper endoscopy with biopsies PROCEDURE

Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing

5. Gastric cancer; 6. Gastric dysplasia; 7. High-risk gastric lesions; 8. Normal and low-risk gastric lesions

Colonoscopy with biopsies or lesion removal when required PROCEDURE

Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing

1. Colorectal cancer; 2. Colorectal high-risk lesions; 3. Colorectal low-risk adenoma; 4. Group of control (colorectal)

Plasma/serum sampling PROCEDURE

Plasma/serum sampling will be used to obtain information for group stratification, e.g. H.pylori status determination

1. Colorectal cancer; 2. Colorectal high-risk lesions; 3. Colorectal low-risk adenoma; 4. Group of control (colorectal); 5. Gastric cancer; 6. Gastric dysplasia; 7. High-risk gastric lesions; 8. Normal and low-risk gastric lesions; 9. Average risk population

Faecal sample acquisition PROCEDURE

Faecal samples will be obtained for faecal occult blood testing as well as microbiota analysis

1. Colorectal cancer; 2. Colorectal high-risk lesions; 3. Colorectal low-risk adenoma; 4. Group of control (colorectal); 5. Gastric cancer; 6. Gastric dysplasia; 7. High-risk gastric lesions; 8. Normal and low-risk gastric lesions; 9. Average risk population

Histological evaluation of the surgery material PROCEDURE

The material obtained during surgery (stomach or colorectal) will be used for confirmation of the diagnosis in cancer groups. Surgery itself will be performed according to the clinical indications, and will not be extended (i.e. cannot be considered a study intervention)

1. Colorectal cancer; 5. Gastric cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cancer patients (Group 1 and 5) will be predominantly enrolled at the time scheduled for surgery, however also patients undergoing diagnostic procedures (endoscopy) will be eligible Patients without malignant disease but defined colorectal (Groups 2-4) status will be predominantly enrolled prior colonoscopy in out-patient settings. Sampling starting from 1 week after colonoscopy will be allowed if the lesions will not get removed during the index endoscopy Patients without malignant disease but defined gastric mucosal status (Groups 6-8) status will be predominantly enrolled prior upper endoscopy in out-patient settings. Sampling starting from 2 days after upper endoscopy will be allowed if the lesions will not get removed during the index endoscopy Average cancer risk subjects (Group 9) will get enrolled by inviting individuals predominantly selected from the lists of general practitioners.

You may qualify if:

• Patients with verifies colorectal cancer (Group 1)
• Patients with verified gastric cancer (Group 5)
• Patients undergoing colonoscopy due to clinical indications (group 2-4)
• Patients undergoing upper endoscopy due to clinical indications (Group 6-8)
• Motivation to participate in the study
• Physical status allowing volatile marker sampling and other procedures within the protocol
• Signed consent

You may not qualify if:

• Known other active cancer
• Ventilation problems, airway obstruction
• Unwillingness or inability to co-operate

Sponsors & Collaborators

• University of Latvia: lead
• Technion, Israel Institute of Technology: collaborator
• Lithuanian University of Health Sciences: collaborator
• Karolinska Institutet: collaborator
• German Cancer Research Center: collaborator
• Digestive Diseases Centre GASTRO: collaborator
• Riga East Clinical University Hospital: collaborator
• Academic Histology Laboratory (Latvia): collaborator
• JLM Innovation GmbH (Germany): collaborator

Study Sites (2)

University of Latvia

Riga, LV 1586, Latvia

Location

Lithuanian University of Health Sciences

Kaunas, LT 44307, Lithuania

Location

Related Publications (3)

• Haick H, Broza YY, Mochalski P, Ruzsanyi V, Amann A. Assessment, origin, and implementation of breath volatile cancer markers. Chem Soc Rev. 2014 Mar 7;43(5):1423-49. doi: 10.1039/c3cs60329f. Epub 2013 Dec 4.

  PMID: 24305596 BACKGROUND

• Xu ZQ, Broza YY, Ionsecu R, Tisch U, Ding L, Liu H, Song Q, Pan YY, Xiong FX, Gu KS, Sun GP, Chen ZD, Leja M, Haick H. A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions. Br J Cancer. 2013 Mar 5;108(4):941-50. doi: 10.1038/bjc.2013.44.

  PMID: 23462808 BACKGROUND

• Amal H, Leja M, Broza YY, Tisch U, Funka K, Liepniece-Karele I, Skapars R, Xu ZQ, Liu H, Haick H. Geographical variation in the exhaled volatile organic compounds. J Breath Res. 2013 Dec;7(4):047102. doi: 10.1088/1752-7155/7/4/047102. Epub 2013 Nov 1.

  PMID: 24184568 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Exhaled air samples being stored in specific adsorbent media Plasma/serum samples for group stratification Faecal samples for occult blood testing and microbiota analysis Biopsy samples from stomach and colon

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Peptic Ulcer; Gastritis, Atrophic; Gastrointestinal Neoplasms; Adenoma

Interventions

Gastroscopy; Biopsy; Colonoscopy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Duodenal Diseases; Gastritis; Gastroenteritis; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Study Officials

• Hossam Haick, Ph.D.

  Technion, Israel Institute for Technology (Israel)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 6, 2015
• Study Start: January 1, 2014
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2017
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

LI (1); LA (1)