Clinical trial NCT04038996: The Role of SNP rs2910164 in Patients Treated With Immune Checkpoint Inhibitors
Official title: A Single-Center, Prospective, Observational Trial to Analyze the Relationship Between Single Nucleotide Polymorphism rs2910164 and the Efficacy and Safety of Immune Checkpoint Inhibitor Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Keywords: immune checkpoint inhibitor
single nucleotide polymorphism
microRNA
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2019-07-31
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with cancer undergoing immune checkpoint inhibitor therapy

Brief summary: The objective of this study is to investigate whether the SNP rs2910164 in the pre-miR-146a gene is associated with outcome and toxicity of immune checkpoint inhibitor therapy.

Detailed description: The single nucleotide polymorphism (SNP) rs2910164 within the gene for microRNA-146a (miR-146a) reduces miR-146a expression. Previous studies of the investigators demonstrated that this SNP was associated with increased acute GvHD severity in patients undergoing allogeneic hematopoietic stem cell transplantation. In this prospective, observational study the investigators aim to analyze, whether SNP rs2910164 is associated with severity of immune-related adverse events of immune checkpoint inhibitor therapy. Moreover, association of rs2910164 with outcome parameters will be studied.

Eligibility criteria: Inclusion Criteria:

* confirmed diagnosis of cancer
* treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1 or anti-CTLA4)
* age ≥ 18 years
* peripheral blood sample available
* written informed consent
* ability to understand the nature of the study and the study related procedures and to comply with them

Exclusion Criteria:

* age \< 18 years
* lack of informed consent

Primary outcomes:
measure: Severity of immune-related adverse events (irAEs)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Freiburg
name: Robert Zeiser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2008 May 20;105(20):7269-74. doi: 10.1073/pnas.0802682105. Epub 2008 May 12.
citation: Stickel N, Hanke K, Marschner D, Prinz G, Kohler M, Melchinger W, Pfeifer D, Schmitt-Graeff A, Brummer T, Heine A, Brossart P, Wolf D, von Bubnoff N, Finke J, Duyster J, Ferrara J, Salzer U, Zeiser R. MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia. 2017 Dec;31(12):2732-2741. doi: 10.1038/leu.2017.137. Epub 2017 May 9.
citation: Marschner D, Falk M, Javorniczky NR, Hanke-Muller K, Rawluk J, Schmitt-Graeff A, Simonetta F, Haring E, Dicks S, Ku M, Duquesne S, Aumann K, Rafei-Shamsabadi D, Meiss F, Marschner P, Boerries M, Negrin RS, Duyster J, Zeiser R, Kohler N. MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight. 2020 Mar 26;5(6):e132334. doi: 10.1172/jci.insight.132334.