Study of Blood Components as Probable Prognostic and Predictive Markers of Response to Treatment in Advanced Colon and Rectal Cancers

NCT02979470 | Unknown DMC

• 1 other identifier: CEP2141/15
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The main reason of cancer-related mortality is the spread of cancer cells to distant sites (micrometastases). However, only a few small groups of tumor cells can metastasize by acquiring mechanism to decrease the immune response. Changes in the systemic inflammatory response to the tumor can be measured by blood-based parameters. In particular, the proportion of neutrophyls- lymphocytes (NL) has been evaluated for predicting the survival of patients with different types of cancer. The first strategy to treat colorectal cancer (CCR) is complete resection of the lesion. Nevertheless, some patients experience recurrence, probably due to residual micrometastases. We have demonstrated that analysis of some resistance proteins (Tyms / MRP1) in circulating tumor cells (CTCs) may predict treatment response in metastatic CCR patients (mCRC). We also note that the CTCs kinetics can show response to therapy. Patients with stage III disease in the colon / rectum, although showing high cure rate, generally fall locally or remotely and studies with blood markers in this group of patients is still scarce. Primary Objective: To investigate cells found in the blood (lymphocytes and neutrophils and CTCs) to verify if they can help in the choice of anti-neoplastic therapy in patients with advanced colon and rectum cancers. Secondary objectives: - to evaluate the influence of CTC kinetics in response to treatment of patients with advanced colon/rectum cancers; - to check the expression of treatment resistance, invasion and proliferation proteins (Tyms, TGF-βR, MMP-2, β-gal, Ki-67 and CD45) in CTCs and their correlation with response to treatment; - to check the mRNA expression of the same genes observed by immunocytochemistry in CTCs and their correlation with response to treatment; - to quantify CTCs, neutrophils and lymphocytes of patients included in this study and verify if there are correlation among their rates and progression-free survival. Methods: there will be collected 10 ml of blood of patients with advanced colon and rectal cancer for analysis of CTCs, lymphocytes / neutrophils. CTCs will be isolated, quantified and analyzed after separation by ISET method (Rarecells/France). The marker analysis of these cells will be done by immunocytochemistry and the gene expression will be assessed by RNAscope. The quantification of lymphocytes/neutrophils will be made by common blood count in Delboni laboratory. Expected Results: We propose to show that not only the count and the kinetics of CTCs, but also their molecular characteristics, can provide relevant information to clinicians. Hopefully, by quantification of neutrophils and lymphocytes, we will be able to identify new prognostic blood biomarkers that can direct clinicians to the best therapeutic choice.

Conditions

Colon Cancer Stage IIb; Rectum Cancer, Adenocarcinoma; Colon Cancer Stage IIIa; Colon Cancer Stage IIIc; Colon Cancer Stage IIIb

Keywords

advanced colon cancer; advanced rectum cancer; circulating tumor cells; immune response; mutations

Outcome Measures

Primary Outcomes (1)

• progression free survival

  time between first blood collection for CTC´s analysis and first progression

  24 months

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

colon (EC III) or rectum (EC II and III) cancer patients

Sponsors & Collaborators

• AC Camargo Cancer Center: lead

Study Sites (1)

ACCamargo Cancer Center

São Paulo, São Paulo, 01509900, Brazil

RECRUITING

Related Publications (2)

• Abdallah EA, Fanelli MF, Souza E Silva V, Machado Netto MC, Gasparini Junior JL, Araujo DV, Ocea LM, Buim ME, Tariki MS, Alves Vda S, Piana de Andrade V, Dettino AL, Abdon Lopes de Mello C, Chinen LT. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer. Int J Cancer. 2016 Aug 15;139(4):890-8. doi: 10.1002/ijc.30082. Epub 2016 Apr 28.

  PMID: 26950035 RESULT

• Abdallah EA, Fanelli MF, Buim ME, Machado Netto MC, Gasparini Junior JL, Souza E Silva V, Dettino AL, Mingues NB, Romero JV, Ocea LM, Rocha BM, Alves VS, Araujo DV, Chinen LT. Thymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients. Int J Cancer. 2015 Sep 15;137(6):1397-405. doi: 10.1002/ijc.29495. Epub 2015 Mar 11.

  PMID: 25721610 RESULT

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Neoplastic Cells, Circulating

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ludmilla Chinen, PhD

  AC Camargo Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ludmilla Chinen, PhD

CONTACT

551121895000; ludmilla.chinen@cipe.accamargo.org.br

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: September 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2019
• Last Updated: July 2, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)