Evaluation of PD1 / PDL1 Expression on Blood Cells & Tumor Tissue, Their Role as a Prognostic Target in NSCLC Patients

Non-Small Cell Lung Cancer Clinical Trial

Official title:

Clinical Pathological Features Associated With the Expression of PD1 / PD-L1 in Subpopulations of Peripheral Blood and Tumor Tissue in Patients With Advanced Non-small Cell Lung Cancer, Their Role as Prognostic and Therapeutic Targets

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02758314
• Other study ID #: INCAN/CI/498/13
• Status: Not yet recruiting
• Phase: N/A
• First received: April 6, 2016
• Last updated: November 23, 2016
• Start date: March 2017
• Est. completion date: December 2018

Study information

• Verified date: November 2016
• Source: Instituto Nacional de Cancerologia de Mexico
• Contact: Oscar Gerardo MD Arrieta Rodriguez, Oncology
• Phone: 01 52 556280400
• Email: ogarrieta[@]gmail.com, ogartsrr[@]yahoo.com.mx
• Is FDA regulated: No
• Health authority: Mexico: Federal Commission for Protection Against Health Risks
• Study type: Observational

Clinical Trial Summary

Several reports have examined Programmed Death 1 (PD-1) expression on tumor-infiltrating T-cells, and its correlation with prognosis has been discussed. However, Programmed Death 1 (PD1)/Programmed Death Ligand 1 (PDL1) expression on the peripheral blood T-cells of cancer patients, particularly in those with lung cancer, has not been sufficiently studied. The purpose of this study is evaluate the expression of PD1 and PDL1 in subpopulations of peripheral blood and tumor cells patients with lung cancer non-small cell (NSCLC), associating with clinicopathological features of the patients studied.

Description:

This is a prospective cohort study including patients with NSCLC stages IIIA, IIIB and IV lung cancer clinic of the National Cancer Institute (INCAN)

Clinical samples. Prior and informed consent before receiving any treatment, sample be obtained 15 ml peripheral blood of each subject included in the study (patients and controls). mononuclear peripheral blood cells (PBMC) from different groups of subjects separated by centrifugation gradient (Polymorphprep, Accurate Chemical) are used. The cells are resuspended in dimethylsulfoxide (DMSO) and 10% fetal bovine serum (FBS) to 90% at a concentration of 1 million cells per ml and kept in liquid nitrogen until use.

Evaluation of PD-1, PD-L1 by flow cytometry. The following monoclonal antibodies directed against cell surface antigens of human are used: anti-PD-1, anti-PD-L1, anti-PD-L2, anti- cluster of differentiation (CD) 3, anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD56, anti-CD19, anti-CD20.

Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC). Lung biopsy is obtained paraffin blocks, and are processed by IHC technique for antitumor expression of PD1 / PDL1.V PD-L1 immunostaining was classified into two groups according to intensity and extent: (a) negative, when no staining or positive staining was detected in <5% of the cells; and (b) positive, when membranous staining was present in P5% of the cells.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria patient :

1. Patients who have understood and signed the informed consent.

2. Diagnosis of lung cancer, histologically or cytologically documented (stage IIIA / B or IV) non-small cell adenocarcinoma, which had not received radiotherapy and / or chemotherapy prior to the first sample.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and evidence of measurable disease.

Exclusion Criteria patient:

1. Subjects with Non-small cell lung cancer with a different histological type to adenocarcinoma.

2. Subjects with acute inflammation and uncontrolled infections.

Inclusion Criteria healthy subjects :

1. Informed consent in writing (signed) to participate in the study.

2. No diagnosis of oncological disease.

3. Subjects without symptoms of any respiratory illness in the two weeks prior to sampling.

Exclusion criteria healthy volunteers.

1. Any unstable systemic disease (including active or metabolic infection, congestive heart failure, liver disease, kidney).

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Other:
• Evaluation of PD-1/PDL-1 expression.
Evaluate the expression of PD-1 / PD-L1 on T-cell subpopulations of peripheral blood by flow cytometry and in tumor tissue by immunohistochemistry in NSCLC, free treatment and healthy subjects

Locations

Country	Name	City	State
Mexico	Instituto National de Cancerologia	Mexico

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancerologia de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (4)

Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013 Oct;14(10):1014-22. doi: 10.1038/ni.2703. Review. — View Citation

Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515-48. Review. — View Citation

Pennock GK, Chow LQ. The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment. Oncologist. 2015 Jul;20(7):812-22. doi: 10.1634/theoncologist.2014-0422. Review. — View Citation

Su M, Huang CX, Dai AP. Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer. Asian Pac J Cancer Prev. 2016;17(3):905-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC)	Immunolocalization of PD-1, PD-L1 in lung tumor tissue of patients with NSCLC. Immunohistochemical staining (IHC). Lung biopsy is obtained paraffin blocks, and are processed by IHC technique for antitumor expression of PD1 / PDL1.V PD-L1 immunostaining was classified into two groups according to intensity and extent: (a) negative, when no staining or positive staining was detected in <5% of the cells; and (b) positive, when membranous staining was present in P5% of the cells.	Baseline evaluation	No
Secondary	Evaluation of PD-1, PD-L1 by flow cytometry.	Evaluation of PD-1, PD-L1 by flow cytometry. The following monoclonal antibodies directed against cell surface antigens of human are used: anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 3 (CD3), anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD56, anti-CD19, anti-CD20.	Baseline evaluation	No