Microbial Diversity Between Inflamed and Non-inflamed Skin of Patients With Immune Checkpoint Inhibitor-Induced Dermatitis

A Single Cohort Study to Characterize Differences in Microbial Diversity Between Inflamed and Non-Inflamed Skin of Patients With Immune Checkpoint Inhibitor-Induced Dermatitis

This study determines microbial diversity between inflamed and non-inflamed skin of patients with immune checkpoint inhibitor-induced dermatitis. Skin has millions of bacteria. When treated with an immunotherapy agent, skin issues like a rash are common, occurring in up to 45% of patients. This study finds out if the type of bacteria on skin is different between the affected and unaffected skin in patients who have this treatment-related rash and also compares the immune cells found in the skin tissue to those seen in the blood.

Study Overview

• Status: Completed
• Conditions: Genito-Urinary Neoplasm
• Intervention / Treatment: Procedure: Biospecimen Collection(Punch Biopsy)

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if skin microbial diversity (estimated by the Shannon Index) significantly differs between inflamed and non-inflamed skin from patients who have immune checkpoint inhibitor (ICI)-induced dermatitis.

SECONDARY OBJECTIVES:

I. To investigate if certain bacterial species and strains are present in higher concentrations of inflamed versus non-inflamed skin of patients with ICI-induced dermatitis.

II. To compare the immune cell phenotypes of inflamed and non-inflamed skin from patients who have ICI-induced dermatitis.

III. To characterize the immune cell phenotype in the peripheral blood in patients who have ICI-induced dermatitis.

IV. To elucidate any association between the skin microbial diversity and response to immunotherapy, characterized by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (e.g., durable complete response [CR] versus partial response [PR] versus stable disease [SD] versus primary progressive disease).

V. To ascertain if higher concentrations of certain bacterial species are associated with a response to immunotherapy, characterized by both RECIST and immune response criteria.

VI. To evaluate associations between the non-inflamed skin flora and cancer subtypes (e.g., renal cell carcinoma, bladder cancer, lung cancer).

VII. To examine if skin microbiome is associated with specific demographic characteristics such as age and gender.

OUTLINE:

Patients undergo punch biopsies of inflamed and non-inflamed skin and a blood sample collection.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical 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

Description

Inclusion Criteria:

• Patients receiving treatment with any of the Food and Drug Administration (FDA) approved monoclonal antibodies that block CTLA-4, PD-1, PD-L1, or any combination thereof
• Patients recommended to undergo skin biopsy due to a clinical diagnosis of ICI-induced dermatitis as part of routine and standard clinical care are eligible
• Patients must be age 18 or older
• Eastern Cooperative Oncology Group (ECOG) performance status < 2
• Measurable disease as per RECIST 1.1
• Patients must be able to personally sign and date informed consent indicating that the patient has been informed of all pertinent aspects of the study are eligible

Exclusion Criteria:

• Patients taking antibiotics or who plan to begin taking antibiotics
• Use of topical or systemic steroids within the past 14 days. Inhaled steroids are permitted
• Known medical condition (e.g. a disease associated with chronic skin inflammation such as atopic dermatitis or psoriasis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of results
• Not recovered to non-dermatologic =< grade 1 toxicities related to any prior therapy
• Pregnant woman will not be enrolled in this study. It is a regulatory requirement that for studies that carry no prospect of benefit to the woman, the research can only enroll pregnant women if the resulting knowledge cannot be obtained by any other means. In this study, there is no prospect of direct benefit to the pregnant women
• Patients with human immunodeficiency virus (HIV), hepatitis B, or C will be excluded from this study
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures (including compliance issues related to feasibility/logistics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Skin Biopsies; Patients undergo punch biopsies of inflamed and non-inflamed skin and a blood sample collection.	Procedure: Biospecimen Collection(Punch Biopsy); Punch Biopsy of Skin; Other Names: Biospecimen Collection (Punch Biopsy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between skin microbial diversity and immune checkpoint inhibitor (ICI)-induced dermatitis	Microbial diversity will be estimated by the Shannon Index.	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin microbial diversity	Will be associated with response to therapy. The non-flamed skin of responders versus non-responders will be compared against change in Shannon Index. Both parametric and non-parametric tests will be performed on the data as well as its log-transformation.	Up to 1 year
Abundances of certain skin bacteria in lesion	Will be associated with a higher rate of dermatologic toxicity with ICI. Similar to the evaluation of microbial diversity, will evaluate the concentrations of specific bacteria of inflamed as compared to non-inflamed skin of a similar phenotype (e.g. sebaceous, moist, or dry). This will entail both an individual bacteria abundance evaluation and clustering analysis.	Up to 1 year
Specific skin bacteria	Will be associated with higher response to ICI. Will evaluate specific bacteriomic differences between the responders and non-responders via individual bacteria abundance assessment and clustering analysis. Response will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and assessed at the time of each skin biopsy. This will entail both an individual bacteria abundance evaluation and clustering analysis.	Up to 1 year
Tissue and peripheral immune cell phenotypes of ICI-induced dermatitis (I)	Will use immunohistochemistry to aid in characterizing the dermatologic microenvironment as follows: will use immunohistochemistry to aid in characterizing the dermatologic microenvironment. The Human Cytokine 30-plex protein assay (Invitrogen) will be used to characterize the plasma levels of cytokines in pg/mL.	Up to 1 year
Tissue and peripheral immune cell phenotypes of ICI-induced dermatitis (II)	Will use immunohistochemistry to aid in characterizing the dermatologic microenvironment as follows: will use immunohistochemistry to aid in characterizing the dermatologic microenvironment. Fluorochrome-labeled antibodies will be used to characterize the number of myeloid cells.	Up to 1 year
Tissue and peripheral immune cell phenotypes of ICI-induced dermatitis (III)	Will use immunohistochemistry to aid in characterizing the dermatologic microenvironment as follows: will use immunohistochemistry to aid in characterizing the dermatologic microenvironment. EasySep PE-selection kit will be used to characterize the number of T cells.	Up to 1 year

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Actual): October 8, 2021
• Study Completion (Actual): October 8, 2021

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Dermatitis; Urogenital Neoplasms
• Other Study ID Numbers: 20378 (City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2021-00221 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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