Clinical trial NCT02654288: Dynamic Changes of Sera Immunoglobulin G4 and Interleukin-10 in the Patients of Pancreatic Cancer After Chemotherapy
Official title: Dynamic Changes of the Serum Level of Immunoglobulin G4(IgG4) and Interleukin-10(IL-10) in the Patients of Pancreatic Cancer After Gemcitabine-based Chemotherapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pancreatic Neoplasms
Inflammation
Keywords: pancreatic cancer
gemcitabine
chemotherapy
immunoglobulin G 4
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2016-01-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pancreatic cancer patients without history of chemotherapy will be recruited. After evulation of the physical status, the patients will receive gemcitabine-based chemotherapy.The peripheral blood will be collected and the sera IgG4 and IL-10 will be detected during chemotherapy. Then the correlation of the dynamic changes of IgG4 and IL-10 with the response of chemotherapy and the overall survival will be analyzed.

Brief summary: Investigators have previously found that the infiltration of immunoglobulin G4(IgG4) positive plasma cells in tumor tissue predicts a poor prognosis of pancreatic cancer after curative resection. Investigators further attempt to explore the possible roles of IgG4 and the inducer of IgG4, interleukin-10(IL-10), in the chemotherapy of pancreatic cancer. In this primary study, investigators plan to observe the dynamic changes of sera IgG4 and IL-10 in peripheral blood after gemcitabine-based chemotherapy and analyze the correlations of IgG4 and IL-10 with the response of gemcitabine and overall survival of pancreatic cancer.

Detailed description: Human immunoglobulin G(IgG) is a family consisting of four members, IgG1, IgG2, IgG3 and IgG4.IgG4 is regarded as an inhibitory IgG which can inhibit the activation of immune responses\[1\]. Recently it was reported that IgG4 could weaken the activation of macrophages to promote cancer progression\[2\]. Autoimmune pancreatitis(AIP) is the most common clinical manifestation of IgG4-related sclerosing diseases(IRSD) which is characterized by abundant infiltration of IgG4 positive plasma cells\[3\].Although there are abundant infiltrations of IgG4 positive plasma cells in pancreatic lesion of AIP, the correlation of IgG4 positive plasma cells with pancreatic cancer has never been reported.Investigators have previously found that higher level of infiltration of IgG4 positive plasma cells in tumor tissue predicts a poor prognosis of pancreatic cancer after curative resection(not published).Investigators further attempt to explore the possible roles of IgG4 and the inducer of IgG4, IL-10, in the chemotherapy of pancreatic cancer.Since gemcitabine is the first line chemotherapeutic drug for pancreatic cancer, in this primary study,investigators plan to observe the dynamic changes of sera IgG4 and IL-10 in peripheral blood after gemcitabine-based chemotherapy and analyze the correlations of IgG4 and IL-10 with the response of gemcitabine and overall survival of pancreatic cancer.

Eligibility criteria: Inclusion Criteria:

1. Age ranging from 18 to 75-year old;
2. Pathological verified pancreatic cancer including adenocarcinoma and cancerogenesis of intraductal papillary mucinous neoplasm (IPMN);
3. Pancreatic cancer patients receiving adjuvant chemotherapy after curative resection; pancreatic cancer patients with recurrent lesions receiving chemotherapy after curative resection; pancreatic cancer patients with unresectable tumor receiving chemotherapy;
4. Patients have good physical status to receive chemotherapy;
5. No history of chemotherapy and the current regimen contains gemcitabine;
6. No medical history of IgG4 related diseases and other connective tissue diseases;
7. Written consent is available.

Exclusion Criteria:

1. Patient younger than 18-year old;
2. Patient has chemotherapy before;
3. The physical status is too poor to receive chemotherapy;
4. The patient has history of IgG4 related diseases and some other connective diseases;
5. Written consent is not available.

Primary outcomes:
measure: The dynamic change patterns of sera IgG4 and IL-10 of pancreatic cancer after gemcitabine-based chemotherapy will be recorded.
timeFrame: one year
Secondary outcomes:
measure: The correlation of the changes of IgG4 and IL-10 with the tumor marker during chemotherapy will be analyzed
timeFrame: one year
measure: The correlation of the changes of IgG4 and IL-10 with the efficacy of chemotherapy evaluated by intravenous enhanced CT during chemotherapy will be analyzed
timeFrame: one year
measure: The correlation of the changes of IgG4 and IL-10 with the overall survival after chemotherapy will be analyzed.
timeFrame: Two year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences
name: Quan Liao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davies AM, Sutton BJ. Human IgG4: a structural perspective. Immunol Rev. 2015 Nov;268(1):139-59. doi: 10.1111/imr.12349.
citation: Karagiannis P, Villanova F, Josephs DH, Correa I, Van Hemelrijck M, Hobbs C, Saul L, Egbuniwe IU, Tosi I, Ilieva KM, Kent E, Calonje E, Harries M, Fentiman I, Taylor-Papadimitriou J, Burchell J, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology. 2015 Jun 3;4(11):e1032492. doi: 10.1080/2162402X.2015.1032492. eCollection 2015 Nov.
citation: Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L, Correa I, Roberts L, Beddowes E, Koers A, Hobbs C, Ferreira S, Geh JL, Healy C, Harries M, Acland KM, Blower PJ, Mitchell T, Fear DJ, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest. 2013 Apr;123(4):1457-74. doi: 10.1172/JCI65579.