Clinical trial NCT04734067: Exploration of the Predictive Marker and Establishment of Predictive Models of Checkpoint Inhibitor Pneumonitis
Official title: Exploration of Predictive Markers and Establishment of Predictive Models for Checkpoint Inhibitor Pneumonitis in Combination With Imaging in Immune Checkpoint Inhibitor Therapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pneumonia, Interstitial
Keywords: immune checkpoint inhibitors
predictive marker
predictive model
immunotherapy
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Tang-Du Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Henan Cancer Hospital
name: Wuhan Union Hospital, China
name: Fujian Cancer Hospital
First posted: 2021-02-02
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with malignant tumor receiving immune checkpoint inhibitors for the first time.

Brief summary: This is a prospective, multicenter observational study to explore the predictive factors of checkpoint inhibitor pneumonitis (CIP) and to establish predictive models by combining imaging information for IRP. The imaging type of CIP, the pathological type, various inflammatory cytokines and tumor proportion score(TPS) of PD-L1 expression level, etc. will be paid more attention.

Detailed description: Prospective dual-arm, multicenter observational study to explore the predictive factors of checkpoint inhibitor pneumonitis (CIP) and to establish predictive models by combining imaging information.Patients will receive work-up, treatment and follow-up exclusively as routinely done except monitoring and evaluation of CIP. Necessary tests will be required, such as lung function tests, lymphocyte subsets, and thin-section CT of the chest during evaluation of the disease.This study mainly included patients with malignant tumor who received immune checkpoint inhibitors for the first time.Fasting venous blood was taken before treatment and before cycle 3,5...2n+1 of treatment. Then the blood samples were centrifuged and frozen in a refrigerator at -80℃ for later mass spectrometry analysis. IrAEs of patients was strictly recorded according to CommonTerminology Criteria Adverse Events V4.0 (CTCAE V4.0). The main objective was to explore the relationship between various indicators and the occurrence of CIP, including pulmonary ventilation and diffusion function at baseline, C-reative protein(CRP), cytokines, interleukin-6(IL-6), CD4+ T lymphocyte count and percentage, CD8+ T lymphocyte count and percentage, NK cell count and percentage, total T lymphocyte count and percentage, neutrophil counts and percentages, eosinophilic cell count and percentage, white blood cell count, blood platelet count, serum albumin(ALB), alanine aminotransferase(ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase（γ-GGT), body mass index (BMI), serum procalcitonin(PCT), smoking index and various inflammatory cytokines.

Primary study endpoints: The predictive factors and the predictive models of CIP.

Secondary study endpoints: The incidence and clinical characteristics of CIP.

Eligibility criteria: Inclusion Criteria:

* age ≥ 18 years;
* Obtain written informed consent and any locally required authorization from the patient or his/her legal representative prior to the commencement of any study protocol related procedures, including screening assessments;
* Patients with malignant tumors confirmed by histology or cytology can be treated with ICIs after evaluation by a professional oncologist, with no restriction on cancer type or stage;
* Life expectancy on day 1 ≥12 weeks;
* When selected, the Eastern Cooperative Oncology Group (ECOG) physical status score was 0-2;
* No previous use of immunotherapy；
* No prior exposure to immune-mediated therapy;
* Have sufficient viscera function and bone marrow function;
* Evidence of postmenopausal status in women, or negative urine or serum pregnancy tests in premenopausal women.

Exclusion Criteria:

* The target lesion had received immune-related treatment or immune-mediated treatment before;
* Patients with clinically confirmed moderate to severe pulmonary interstitial fibrosis before taking ICIs;
* Major surgical procedures were performed within 28 days of the first medication;
* History of allograft transplantation;
* Active or previously documented autoimmune or inflammatory diseases or other contraindications for immunotherapy;
* Uncontrolled serious complications such as infection and acute cardio-cerebrovascular disease;
* The presence of another primary malignancy;
* anaphylaxis or hypersensitivity to immunotherapy or chemotherapy;
* Decompensation of viscera and low bone marrow function and hematopoietic function；
* Pregnant or lactating female patients;
* Expected survival time \< 3 months

Primary outcomes:
measure: The change of C reactive protein(CRP); mg/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Interleukin-6(IL-6); Pg/ml
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: CD4+ T lymphocyte; /uL
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: CD4+ T lymphocyte; percent
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: CD8+ T lymphocyte; /uL
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: CD8+ T lymphocyte; percent
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: NK cell; /uL
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: NK cell; percent
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: White blood cell count; 10^9/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Lymphocyte count; 10^9/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Lymphocyte count; percent
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Eosinophils count; 10^9/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Eosinophils count; percent
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Blood platelet count; 10^9/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Alanine aminotransferase(ALT); U/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Aspartate aminotransferase (AST); U/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Serum albumin; g/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: γ-glutamyl transpeptadase（γ-GGT); U/L
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Smoking index
timeFrame: At baseline
measure: Body mass index (BMI); kg/m^2
timeFrame: At baseline
measure: Serum procalcitonin(PCT); ng/ml
timeFrame: Before Cycle 1,3, 5, 7 and 2n+1(each cycle is 21 days) and through study completion, an average of 6 months.
measure: Forced vital capacity(FVC); L
timeFrame: Before Cycle 1.
measure: Forced the first second of expiratory volume (FEV1); L
timeFrame: Before Cycle 1.
measure: FEV1/FVC; percent
timeFrame: Before Cycle 1.
measure: Maximal mid-expiratory flow(MMEF); L/s
timeFrame: Before Cycle 1.
measure: Fractional exhaled nitric oxide (FeNO) measurement；ppb
timeFrame: Before Cycle 1.
Secondary outcomes:
measure: The incidence of IRP; percent
timeFrame: Up to 36 months
Other outcomes:
Locations:
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Hui Guo, PH.D
role: PRINCIPAL_INVESTIGATOR
References: