Personalizing Immune Checkpoint Inhibitor Therapy

Lung Cancer Stage IV Clinical Trial

Official title:

Personalizing Immune Checkpoint Inhibitor Therapy for Solid Tumors

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03409341
• Other study ID #: IRB# 2018-02
• Status: Withdrawn
• Start date: February 1, 2019
• Est. completion date: September 22, 2020

Study information

• Verified date: September 2020
• Source: Holy Cross Hospital, Maryland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This prospective, observational study will evaluate whether vitro testing of tumor tissue and white blood cells from patients with lung cancer who are being treated with immune checkpoint inhibitors and other standard of care approaches, predicts clinical response to these agents.

Description:

Overall Goal: The long-term goal of this study is to predict whether checkpoint inhibitors will be effective in individual patients with solid tumors.

Objectives: In this pilot study to be conducted in ten subjects with lung cancer who are to receive checkpoint inhibitors, we will use cellular and molecular techniques to characterize

• tumor immunogenicity

• anti-tumor T-cell response

• effect of checkpoint inhibitors on antigen presentation and T-cell response, and

• the tumor microenvironment

Planned enrollment:

• Ten subjects with lung cancer

Methods for Informed Consent:

Investigators will approach subjects for informed consent

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 22, 2020
• Est. primary completion date: January 8, 2020
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Subjects with lung cancer about to undergo diagnostic/excisional biopsy with the intent to receive therapy with immune checkpoint inhibitors

• Availability of fresh tumor tissue removed at excisional biopsy or diagnostic biopsy

• Informed consent

Exclusion Criteria:

• Lack of informed consent

Related Conditions & MeSH terms

• Lung Cancer Stage IV

Intervention

Other:
• Blood and tumor tissue analysis, Clinical response.
DNA sequencing and functional testing of peripheral blood mononuclear cells. DNA and RNA sequencing and immune cell analysis of tumor. Clinical response at 12 months.

Locations

Country	Name	City	State
United States	Holy Cross Hospital	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Holy Cross Hospital, Maryland

Country where clinical trial is conducted

United States, 

References & Publications (6)

Ashokkumar C, Talukdar A, Sun Q, Higgs BW, Janosky J, Wilson P, Mazariegos G, Jaffe R, Demetris A, Dobberstein J, Soltys K, Bond G, Thomson AW, Zeevi A, Sindhi R. Allospecific CD154+ T cells associate with rejection risk after pediatric liver transplantation. Am J Transplant. 2009 Jan;9(1):179-91. doi: 10.1111/j.1600-6143.2008.02459.x. Epub 2008 Oct 31. — View Citation

Cruz RJ Jr, Ranganathan S, Mazariegos G, Soltys K, Nayyar N, Sun Q, Bond G, Shaw PH, Haberman K, Krishnamurti L, Marsh JW, Humar A, Sindhi R. Analysis of national and single-center incidence and survival after liver transplantation for hepatoblastoma: new trends and future opportunities. Surgery. 2013 Feb;153(2):150-9. doi: 10.1016/j.surg.2012.11.006. — View Citation

Ningappa M, Ashokkumar C, Higgs BW, Sun Q, Jaffe R, Mazariegos G, Li D, Weeks DE, Subramaniam S, Ferrell R, Hakonarson H, Sindhi R. Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection. Am J Transplant. 2016 Feb;16(2):497-508. doi: 10.1111/ajt.13509. Epub 2015 Dec 11. — View Citation

Ranganathan S, Ningappa M, Ashokkumar C, Higgs BW, Min J, Sun Q, Schmitt L, Subramaniam S, Hakonarson H, Sindhi R. Loss of EGFR-ASAP1 signaling in metastatic and unresectable hepatoblastoma. Sci Rep. 2016 Dec 2;6:38347. doi: 10.1038/srep38347. — View Citation

Sindhi R, Ashokkumar C, Higgs BW. Cellular alloresponses for rejection-risk assessment after pediatric transplantation. Curr Opin Organ Transplant. 2011 Oct;16(5):515-21. doi: 10.1097/MOT.0b013e32834a94e3. Review. — View Citation

Vinayak R, Cruz RJ Jr, Ranganathan S, Mohanka R, Mazariegos G, Soltys K, Bond G, Tadros S, Humar A, Marsh JW, Selby RR, Reyes J, Sun Q, Haberman K, Sindhi R. Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015). Liver Transpl. 2017 Dec;23(12):1577-1588. doi: 10.1002/lt.24847. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tumor immune response	Tumor antigen presentation and anti-tumor T-cell response	12 months
Secondary	Clinical response	Clinical response is defined as 50% or greater decrease of the sum of the products of two-dimensional measurements of lesions on imaging within the first year.	12 months for each subject
Secondary	Tumor microenvironment	Tumor mutation burden from tumor genome landscape using DNA sequencing, tumor transcriptome with RNA sequencing, tumor infiltrating immune cells with flow cytometry	24 months total study duration