The Predictive Value of Cytokines on Response to Preoperative Chemoradiotherapy in Patients With Rectal Cancer

Rectal Cancer Clinical Trial

— CYTORECT  

Official title:

The Predictive Value of Cytokines on Response to Preoperative Chemoradiotherapy in Patients With Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02077296
• Other study ID #: NL46983.100.13/R13.044
• Status: Completed
• Phase: N/A
• First received: February 26, 2014
• Last updated: September 8, 2016
• Start date: March 2014
• Est. completion date: August 2016

Study information

• Verified date: September 2016
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial Summary

Rationale and background: Predictive factors are needed to discriminate chemoradiotherapy responders from non-responders and to individualize the treatment regime. Various cytokines play a role in processes affecting tumour growth and metastasis. Furthermore, cytokines might influence treatment response. Various cytokines are abnormally expressed in colorectal cancer patients, are associated with colorectal cancer or determine response to chemoradiotherapy. Therefore the investigators want to investigate whether levels of circulating cytokines could predict response to preoperative chemoradiotherapy in patients with rectal cancer.

Hypothesis: The investigators hypothesis is that the varying levels of circulating cytokines in the blood of rectal cancer patients may predict the response to preoperative chemoradiotherapy.

Study design: This study is an explorative clinical pilot study in which the investigators will collect 4 ml of blood from a selection of rectal cancer patients during a regular venipuncture before, during and after preoperative chemoradiotherapy and before and after surgery. Cytokines will be measured in blood plasma and in tumour and healthy tissue from the resection specimen using multiplex immunoassays. Plasma cytokine measurements will be linked to pathological response to identify which cytokines and corresponding levels can predict response to preoperative chemoradiotherapy for patients with locally advanced rectal cancer. Furthermore, blood plasma cytokine measurements before and after surgery will be compared to evaluate the effect of tumour resection on the immune response. In addition, preoperative blood plasma cytokine levels will be compared with cytokine levels in normal and tumour tissue to test whether circulating cytokine levels are representative for tissue cytokine levels.

Study population: Thirty patients (≥18 years) with locally advanced rectal adenocarcinoma eligible for preoperative chemoradiotherapy (oral capecitabine and 45-50 gray (Gy) in total; fractions of 1.8-2 Gy) and surgery.

Country of recruitment: The Netherlands

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathohistological diagnosis of locally advanced rectal adenocarcinoma (<15 cm from the anal verge)

• Eligible for preoperative chemoradiotherapy (chemotherapy: oral capecitabine / radiotherapy: 45-50 Gy in total; fractions of 1.8-2 Gy) and surgery (stage 2 or 3 rectal cancer)

• Planned to undergo a venipuncture for a regular blood collection during preoperative chemoradiotherapy, before, and after surgery

• Written informed consent

• Age =18

Exclusion Criteria:

• Age <18

• Serious adverse events during preoperative chemoradiotherapy

• Use of corticosteroids and/or immunosuppressive drugs during or 1 month prior to the study

• Other malignancies in medical history

• Previous pelvic radiotherapy and/or chemotherapy

• Confirmed bacterial or viral infection during the study or 3 months prior to the study

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Locations

Country	Name	City	State
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

Debucquoy A, Haustermans K, Daemen A, Aydin S, Libbrecht L, Gevaert O, De Moor B, Tejpar S, McBride WH, Penninckx F, Scalliet P, Stroh C, Vlassak S, Sempoux C, Machiels JP. Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer. J Clin Oncol. 2009 Jun 10;27(17):2751-7. doi: 10.1200/JCO.2008.18.5033. Epub 2009 Mar 30. — View Citation

Kinoshita T, Ito H, Miki C. Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma. Cancer. 1999 Jun 15;85(12):2526-31. — View Citation

Lin CC, Liu CY, Chen MJ, Wang TE, Chu CH, Wang HY, Shih SC, Hsu ML, Hsu TC, Chen YJ. Profiles of circulating endothelial cells and serum cytokines during adjuvant chemoradiation in rectal cancer patients. Clin Transl Oncol. 2013 Oct;15(10):855-60. doi: 10.1007/s12094-013-1004-6. Epub 2013 Feb 12. — View Citation

Trikha M, Corringham R, Klein B, Rossi JF. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res. 2003 Oct 15;9(13):4653-65. Review. — View Citation

Tsavaris N, Voutsas IF, Kosmas C, Gritzapis AD, Baxevanis CN. Combined treatment with bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients. Invest New Drugs. 2012 Feb;30(1):395-402. doi: 10.1007/s10637-010-9533-0. Epub 2010 Sep 7. — View Citation

Xynos ID, Karadima ML, Voutsas IF, Amptoulach S, Skopelitis E, Kosmas C, Gritzapis AD, Tsavaris N. Chemotherapy ± cetuximab modulates peripheral immune responses in metastatic colorectal cancer. Oncology. 2013;84(5):273-83. doi: 10.1159/000343282. Epub 2013 Feb 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma and tissue cytokine levels	Patients will be followed for the duration of preoperative chemoradiotherapy until 6 weeks after surgery	20 weeks	No