Cancer, Treatment-Related, Immune Checkpoint Inhibitors, Lung Cancer, Sleep Disturbance
Conditions
Keywords
Lung Cancer, Immune Checkpoint Inhibitors, Sleep Disturbance, Circadian Rhythm, Cancer Progression, Prognosis, Biomarker
Brief summary
This is the prospective, observational cohort study (Nezha) to explore the associations of sleep disturbance with progression, efficacy of immune checkpoint inhibitors (ICIs) and prognosis of Lung Cancer. The participants including the patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who received either first-line therapy (ICIs or targeted agents) or neoadjuvant therapy with ICIs; patients diagnosed with advanced small-cell lung cancer (SCLC) receiving the first-line therapy ICIs; patients diagnosed with early non-small-cell lung cancer (NSCLC) receiving surgery.
Detailed description
This is the prospective, observational cohort study (Nezha) to explore the associations of sleep disturbance with progression, efficacy of ICIs and prognosis of Lung Cancer. This study will have 5 cohorts * Cohort 1: A prospective, observational cohort study to explore the association between sleep disturbance and the efficacy of first-line treatment of ICIs in advanced NSCLC. * Cohort 2: A prospective, observational cohort study to explore the association between sleep disturbance and the efficacy of first-line treatment of limited-stage and extensive-stage SCLC. * Cohort 3: A prospective, observational cohort study to explore the association between sleep disturbance and the efficacy of neoadjuvant therapy of ICIs in resectable NSCLC. * Cohort 4: A prospective, observational cohort study to explore the association of sleep disturbance with postoperative recurrence and prognosis in early-stage NSCLC receiving radical surgery. * Cohort 5: A prospective observational cohort study to explore the association between sleep disturbance and the efficacy of first-line treatment of targeted therapy in advanced NSCLC.
Interventions
OTHERExposure: sleep disturbance status
The assessment of sleep disturbance was conducted using Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). Patients with a PSQI score \> 5 or an ISI score \> 7 were categorized as sleep disturbance patients. The assessment of chronotype was conducted using reduced Morningness-Eveningness Questionnaire (rMEQ). Patients with an rMEQ score 18-25 were categorized as the morning type, those with an rMEQ score 12-17 as the intermediate type, and those with an rMEQ score 4-11 as the evening type.
Sponsors
Second Xiangya Hospital of Central South University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort 1: Inclusion Criteria: 1. Age ≥ 18 years old; 2. Histologically confirmed diagnosis of NSCLC; 3. Unresectable locally advanced, metastatic, or recurrent stage ⅢB-Ⅳ based on AJCC TNM staging 8th edition; 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1; 5. Treatment naïve; 6. Presence of at least one measurable lesion according to the Response Evaluation Criteria in Advanced Solid Tumors version 1.1 (RECIST v1.1); 7. Receiving PD-1/PD-L1 inhibitors monotherapy or combination with chemotherapy; 8. Informed consent to participate in the study;
Exclusion criteria
1. Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) fusion and/or ROS proto-oncogene 1 (ROS1) fusion-positive; 2. Presence of other malignant tumors or malignant diseases within 3 years; 3. Concurrent acute or chronic psychiatric disorders; 4. Patients receiving sleep medication; 5. Prior participation in other clinical drug trials; 6. Symptomatic brain metastasis; 7. Inability to complete scale assessments. Cohort 2: Inclusion Criteria: 1. Age ≥ 18 years old; 2. Histologically confirmed diagnosis of SCLC； 3. Unresectable locally advanced, metastatic, or recurrent stage Ⅲ-Ⅳ based on AJCC TNM staging 8th edition; 4. ECOG PS of 0-1; 5. Treatment naïve; 6. Presence of at least one measurable lesion according to the RECIST v1.1 ; 7. Receiving PD-1/PD-L1 inhibitors monotherapy or combination with chemotherapy; 8. Informed consent to participate in the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 2: Overall survival (OS) | 5 years | Duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status. |
| Cohort 3: Event-free survival (EFS) | 3 years | Time from the start of initial treatment of immunotherapy to the occurrence of any event, including disease progression, discontinuation of treatment for any reason, or death. |
| Cohort 4: Disease-free survival (DFS) | 5 years | Duration between the date after surgery to the date of any recurrence or death firstly. |
| Cohort 1 & 5: Progression-free survival (PFS) | 3 years | Time from the beginning of first-line immunotherapy or targeted therapy to the first progression (PD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 3: Pathologic complete response (pCR) rate | 3 years | pCR is no viable tumor cells in tumor bed and lymph nodes. The pCR rate is the proportion of patients with a pathologic complete response. |
| Cohort 3: Major pathologic response (MPR) | 3 years | MPR refers to the percentage of surviving tumor cells in the tumor bed after neoadjuvant therapy ≤10%, regardless of whether there are surviving tumor cells in the lymph nodes. |
| Cohort 1 & 2 & 5: Objective Response Rate (ORR) | 2 years | The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |
| Cohort 1 & 3 & 4 & 5: Overall survival (OS) | 5 years | Overall Survival (OS) is defined as the duration from the start of initial treatment (systemic treatment or radical therapy) until death from any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status. |
| Cohort 2: Progression-free survival (PFS) | 3 years | Time from the beginning of first-line immunotherapy to the first progression (PD). |
| Quality of life (QoL) | 5 years | Quality of life (QoL) is assessed longitude by EORTC QLQ-C30 (version.3). The EORTC QLQ-C30 is composed of 9 multi-item scales: 5 functioning scales (physical, role, cognitive, emotional, and social), a global QOL scale, and 3 symptom scales (fatigue, pain, and nausea/vomiting). All scales and single items are linearly transformed to an 0-100 scale. A higher score represents a better level of functioning. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gut microbiota signature | 5 years | The baseline fetal is collected and assessed by 16S rRNA sequencing to explore the association between gut microbiota, states of sleep disturbance and efficacy and prognosis. |
| Peripheral blood biomarker and immune cells signature | 5 years | The baseline peripheral venous blood is collected. Sleep-related biomarkers (including melatonin, epinephrine, norepinephrine, cortisol, serotonin, dopamine, and endorphins) are measured. The peripheral immune cells signature is assessed by flow cytometry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and dendritic cells (DCs). And explore the associations between peripheral blood biomarkers, immune cells signature, states of sleep disturbance and efficacy and prognosis. |
| Tumor microenvironment signature | 5 years | The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, single-cell sequencing, and spatial transcriptome sequencing to explore the association between tumor microenvironment signature, states of sleep disturbance and efficacy and prognosis. |
Countries
China
Contacts
Primary ContactFang Wu, MD. PhD
Outcome results
None listed