Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers

Colon Cancer Clinical Trial

Official title:

Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02789709
• Other study ID #: PI15/00458
• Status: Recruiting
• Phase: N/A
• First received: May 30, 2016
• Last updated: May 30, 2016
• Start date: January 2016
• Est. completion date: December 2019

Study information

• Verified date: May 2016
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colon Cancer

Intervention

Procedure:
• Surgery
Segmental resection for colon cancer and anterior resection in patients with rectal cancer

Locations

Country	Name	City	State
Spain	Hospital del Mar Medical Research Institute	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Parc de Salut Mar	University of Barcelona

Country where clinical trial is conducted

Spain, 

References & Publications (7)

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 thi — View 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: 10.101 — View Citation

Espín 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. — View Citation

Pascual M, Alonso S, Parés 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 — View 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 — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	Time from the date of surgery to the date of first documentation of recurrence	5 years from the date of surgery	No
Secondary	Disease-specific survival	Time from the date of surgery to death by colon cancer	5 years from the date of surgery	No
Secondary	Local recurrence	Tumor associated with surgical site (anastomosis, tumor bed, and mesentery) and confirmed histologically or by imaging.	5 years from the date of surgery	No
Secondary	Systemic recurrence	Spread of the disease outside the surgical field to organs such as the liver, lungs, bones, or brain	5 years from the date of surgery	No
Secondary	Postoperative intra-abdominal sepsis	Anastomotic leak or intra-abdominal abscess	30 days from the date of surgery	No
Secondary	Postoperative mortality		30 days from the date of surgery	No