Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy

This protocol is a prospective, observational study of participants receiving immunotherapy (checkpoint inhibitors, CPI) for cancer therapy, testing the hypothesis that patients with immune related cutaneous adverse events (ircAEs) have unique immunologic endotypes associated with polarized immune responses.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: systemic corticosteroid or biologic

• Study Type: Observational
• Enrollment (Anticipated): 238

Contacts and Locations

• Study Contact: Name: Jessica Sussman; Phone Number: 303-398-1717; Email: sussmanj@njhealth.org

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health and University of Colorado Denver
      • Contact: Cole Waliczek; Phone Number: 303-270-2488; Email: waliczekt@njhealth.org
      • Principal Investigator: Jeffrey Kern, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult male or female with diagnosis of solid tumor

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, >18 yo
4. Diagnosis of solid tumor including, but not limited to, genitourinary/gynecologic, lung, gastrointestinal and melanoma
5. Receiving, or prior to starting on, a checkpoint inhibitor
6. Grade ≥ 2 ircAE (CTCAE v 5.0) (for cohort 1 only)
7. An indication for system corticosteroids or biologic therapies as determined by the treating physician (for cohort 1 only)
8. Life expectancy ≥ 12 weeks

Exclusion Criteria:

1. Daily use of systemic steroid treatment in the past 4 weeks (prednisone >10mg a day or equivalent) except for indications other than the cutaneous adverse event, and/or as an anti-emetic pre- or post-chemotherapy infusions.
2. Enrollment in any investigational drug trial with a drug that has not been approved
3. Taking other checkpoint inhibitors beyond anti-PD-(L)-1 or anti-CTLA-4 not yet indicated/approved for use
4. Pregnancy
5. Known blood borne infectious disease
6. Current or pervious diagnosis of a leukemia or lymphoma
7. Unable to give consent for study participation
8. Life expectancy < 12 weeks
9. Any other condition or diagnosis in the opinion of the investigator that would interfere with the study results

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CPI with ircAE; Participants on check point inhibitors with immune related cutaneous adverse event	Drug: systemic corticosteroid or biologic; Treatment with systemic corticosteroids or biologic therapies (for corticosteroid refractory patients or these in which corticosteroids are not the treatment of choice)
no ircAE; Participants who do not have a cutaneous adverse event

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Biomarkers	cytokines and chemokines	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of skin and circulating lipid biomarkers which occur during and after ircAEs	Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal	30 days
Mechanisms associated with corticosteroid unresponsiveness in patients with ircAE	Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal	12 months

Collaborators and Investigators

• Sponsor: National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: checkpoint inhibitor; immuno-oncology; cutaneous adverse events
• Other Study ID Numbers: ircAE HS-3411

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No