Clinical trial NCT02789709: Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers
Official title: Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colon Cancer
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: University of Barcelona
First posted: 2016-06-03
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive patients undergoing surgery for colon and rectal cancer with curative intent

Brief summary: Predictive biomarkers are needed to identify those patients with higher risk of recurrence after surgery for colon cancer with curative intent. Our main objective is to determine a metabolite profile in blood plasma from patients operated from colorectal cancer that can be associated with the oncologic outcome and be validated as predictive biomarkers in future studies. A secondary objective is to study the glycolytic metabolism of colon cancer cell lines treated with plasma samples from the same patients. In particular, to validate the increased utilization of lactate by tumor cells as a metabolic substrate using postoperative human samples.

Patients with colorectal cancer that have undergone surgical resection will be included. Plasma samples will be obtained before surgery and the 4th day and the 3rd, 6th, 12th, and 18th months after surgery. Metabolic profiles in plasma samples will be determined using a kit that allows the quantification of 180 metabolites by mass spectrometry.

A clinical follow up will be maintained for at least 2 years to identify tumor recurrences.

Detailed description: Up to 30-40% of patients operated from colorectal cancer display tumor recurrence. Predictive biomarkers are needed to identify those patients with higher risk of recurrence. Our main objective is to determine a metabolite profile in blood plasma from patients operated from colorectal cancer that can be associated with the oncologic outcome and be validated as prognostic biomarkers in future studies. A secondary objective is to study the glycolytic metabolism of colon cancer cell lines treated with plasma samples from the same patients. In particular, to validate the increased utilization of lactate by tumor cells as a metabolic substrate using postoperative human samples, as it was previously observed by us in vitro using an inflammatory environment in conditions of hypoxia and lack of glucose. Patients with colorectal cancer that have undergone surgical resection will be included. Plasma samples will be obtained before surgery and the 4th day and the 3rd, 6th, 12th, and 18th months after surgery. Metabolic profiles in plasma samples will be determined using a kit that allows the quantification of 180 metabolites by mass spectrometry. Cellular assays will be performed on the SW620 and HT-29 colon cancer cell lines. Cells will be treated with plasma samples and the concentration of lactate and other metabolites will be analyzed in the medium supernatants. A clinical follow up will be maintained for at least 2 years to identify tumor recurrences.

Eligibility criteria: Inclusion Criteria:

* Non-metastatic colon and rectal cancer undergoing surgery with curative intent
* Patients signed informed consent

Exclusion Criteria:

* Patients undergoing preoperative chemotherapy and/or radiotherapy
* Emergency surgery
* Surgical resection R1 or R2
* Patients presenting with other known malignancies for which they are receiving treatment

Primary outcomes:
measure: Disease-free survival
timeFrame: 5 years from the date of surgery
Secondary outcomes:
measure: Disease-specific survival
timeFrame: 5 years from the date of surgery
measure: Local recurrence
timeFrame: 5 years from the date of surgery
measure: Systemic recurrence
timeFrame: 5 years from the date of surgery
measure: Postoperative intra-abdominal sepsis
timeFrame: 30 days from the date of surgery
measure: Postoperative mortality
timeFrame: 30 days from the date of surgery
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar Medical Research Institute
Study officials:
References:
citation: Pera M, Nelson H, Rajkumar SV, Young-Fadok TM, Burgart LJ. Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice. J Gastrointest Surg. 2003 Sep-Oct;7(6):783-90. doi: 10.1016/s1091-255x(03)00111-2.
citation: Bohle B, Pera M, Pascual M, Alonso S, Mayol X, Salvado M, Schmidt J, Grande L. Postoperative intra-abdominal infection increases angiogenesis and tumor recurrence after surgical excision of colon cancer in mice. Surgery. 2010 Jan;147(1):120-6. doi: 10.1016/j.surg.2009.06.035. Epub 2009 Sep 20.
citation: Pascual M, Alonso S, Pares D, Courtier R, Gil MJ, Grande L, Pera M. Randomized clinical trial comparing inflammatory and angiogenic response after open versus laparoscopic curative resection for colonic cancer. Br J Surg. 2011 Jan;98(1):50-9. doi: 10.1002/bjs.7258. Epub 2010 Aug 26.
citation: Pascual M, Bohle B, Alonso S, Mayol X, Salvans S, Grande L, Pera M. Preoperative administration of erythropoietin stimulates tumor recurrence after surgical excision of colon cancer in mice by a vascular endothelial growth factor-independent mechanism. J Surg Res. 2013 Jul;183(1):270-7. doi: 10.1016/j.jss.2012.12.041. Epub 2013 Jan 16.
citation: Salvans S, Mayol X, Alonso S, Messeguer R, Pascual M, Mojal S, Grande L, Pera M. Postoperative peritoneal infection enhances migration and invasion capacities of tumor cells in vitro: an insight into the association between anastomotic leak and recurrence after surgery for colorectal cancer. Ann Surg. 2014 Nov;260(5):939-43; discussion 943-4. doi: 10.1097/SLA.0000000000000958.
citation: Espin E, Ciga MA, Pera M, Ortiz H; Spanish Rectal Cancer Project. Oncological outcome following anastomotic leak in rectal surgery. Br J Surg. 2015 Mar;102(4):416-22. doi: 10.1002/bjs.9748. Epub 2015 Jan 26.
citation: Alonso S, Pascual M, Salvans S, Mayol X, Mojal S, Gil MJ, Grande L, Pera M. Postoperative intra-abdominal infection and colorectal cancer recurrence: a prospective matched cohort study of inflammatory and angiogenic responses as mechanisms involved in this association. Eur J Surg Oncol. 2015 Feb;41(2):208-14. doi: 10.1016/j.ejso.2014.10.052. Epub 2014 Nov 1.