The Role of SNP rs2910164 in Patients Treated With Immune Checkpoint Inhibitors

• ClinicalTrials.gov Identifier: NCT04038996
• Recruitment Status: Completed
• First Posted: July 31, 2019
• Last Update Posted: August 20, 2020
• Sponsor: University of Freiburg
• Information provided by (Responsible Party): Robert Zeiser, University of Freiburg

Tracking Information

• First Submitted Date: July 28, 2019
• First Posted Date: July 31, 2019
• Last Update Posted Date: August 20, 2020
• Actual Study Start Date: July 2016
• Actual Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2019)

• Severity of immune-related adverse events (irAEs) [ Time Frame: 2 years ]
  according to CTCAE
• Progression-free survival (PFS) [ Time Frame: 2 years ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

The rs2910164 genotype will be assessed using DNA isolated from peripheral blood samples and Taqman realtime PCR assays.

• Sampling Method: Probability Sample
• Study Population: Adult patients with cancer undergoing immune checkpoint inhibitor therapy
• Condition: Cancer
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• 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.
• Stickel N, Hanke K, Marschner D, Prinz G, Köhler 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.
• Marschner D, Falk M, Javorniczky NR, Hanke-Müller 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, Köhler N. MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight. 2020 Mar 26;5(6). pii: 132334. doi: 10.1172/jci.insight.132334.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2020): 179
• Original Estimated Enrollment (submitted: July 28, 2019): 250
• Actual Study Completion Date: February 2020
• Actual Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04038996
• Other Study ID Numbers: SNP_irAE
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Robert Zeiser, University of Freiburg
• Study Sponsor: University of Freiburg
• Collaborators: Not Provided

Investigators

• Principal Investigator: Robert Zeiser, MD; University of Freiburg

• PRS Account: University of Freiburg
• Verification Date: August 2020