Obstructive Sleep Apnea Influences Efficacy of PD-1-Based Immunotherapy Against Non-Small Cell Lung Cancer

April 24, 2022 updated by: Jing MA, Peking University First Hospital

Obstructive Sleep Apnea Influences Efficacy of Anti-Programmed-Death-1-Based Immunotherapy Against Non-Small Cell Lung Cancer - A Prospective Observational Cohort Study

This prospective, observational cohort study aims to explore the influence of obstructive sleep apnea(OSA) on the efficacy of PD-1-based immunotherapy in patients with non-small cell lung cancer(NSCLC). Patients who had no prior treatment for advanced NSCLC and are intended to receive PD-1/PD-L1 antibody will be recruited. According to sleep monitor results, participants will be divided into Group NSCLC and Group OSA+NSCLC. Primary outcome is the objective remission rate(ORR).

Study Overview

Status

Recruiting

Conditions

Detailed Description

This is a single-center, prospective, observational cohort study. Patients who had no prior treatment for advanced NSCLC and are intended to receive PD-1/PD-L1 antibody will be recruited and followed for 4 years. According to the baseline sleep monitor results, participants will be divided into Group NSCLC(AHI<15), and Group OSA+NSCLC(AHI≥15), and then explore the influence of obstructive sleep apnea on the efficacy of PD-1-based immunotherapy. The baseline level of white blood cell count (WBC); absolute neutrophil count (ANC); absolute lymphocyte count (ALC); ANC to ALC (ANC:ALC) ratio; interleukin 6 (IL-6); C-reactive Protein (CRP) in peripheral blood, lymphocytes classification and count by flow cytometry, and gut microbiome analysis by quantitative metagenomics will also be measured to further search for the possible mechanisms. Primary outcome is the objective remission rate (ORR), secondary outcomes include overall survival (OS) and progression free survival (PFS).

The study protocol has been approved by the Peking University First Hospital Institutional Review Board (IRB). Any protocol modifications will be submitted for the IRB review and approval.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100034
        • Recruiting
        • Peking University First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

Patients who had no prior treatment for advanced NSCLC and are intended to receive PD-1/PD-L1 antibody will be recruited and followed for 4 years.

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed, advanced NSCLC
  2. Participants with no prior treatment for advanced NSCLC
  3. Measurable disease as defined by RECIST v1.1
  4. Eligible to receive first-line treatment including PD-1 antibody
  5. Adequate hematologic and end organ function

Exclusion Criteria:

  1. Severe infection within 4 weeks prior to recruitment.
  2. Significant organ dysfunction or other serious diseases.
  3. Previous or current OSA related treatment, including oral appliance, surgery, mechanical ventilation therapy.
  4. Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Group OSA+NSCLC
According to the baseline sleep monitor results, participants will be divided into Group OSA+NSCLC if apnea hypopnea index(AHI) no less than 15.
Group NSCLC
According to the baseline sleep monitor results, participants will be divided into Group NSCLC if apnea hypopnea index(AHI) less than 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate(ORR)
Time Frame: From date of randomization until the date of first documented progression, assessed up to 48 months
ORR, the percentage of complete response (CR) or partial response (PR) according to RECIST 1.1 standard definition.CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
From date of randomization until the date of first documented progression, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
PFS was defined as the time from recruitment to the first occurrence of progressive disease(PD) or death due to any cause. PD: at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Overall survival (OS)
Time Frame: From date of randomization until the date of death from any cause, assessed up to 48 months
OS was defined as the time from the date of enrollment to the date of death due to any cause.
From date of randomization until the date of death from any cause, assessed up to 48 months
Compared the baseline sleep monitor results between Group NSCLC and Group OSA+NSCLC.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Record baseline AHI, oxygen desaturation index (ODI), lowest saturation by pulse oximetry (SpO2)<90%, obstructive apnea index (OAI), central apnea index(CAI), the longest apnea duration, then compare between Group NSCLC and Group OSA+NSCLC.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Factors associated with ORR in NSCLC patients
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Cox regression analysis will be used to identify predictors of ORR.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Factors associated with OS and PFS in NSCLC patients
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Univariate and multivariate Cox proportional hazards models will be used to identify predictors of PFS and OS.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Compared the baseline level of lymphocytes classification and count between Group NSCLC and Group OSA+NSCLC.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Record baseline lymphocytes classification and count in peripheral blood, then compare between Group NSCLC and Group OSA+NSCLC.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Compared the baseline level of inflammatory biomarkers between Group NSCLC and Group OSA+NSCLC.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Record baseline interleukin 6 (IL-6) and C-reactive Protein (CRP) in peripheral blood, then compare between Group NSCLC and Group OSA+NSCLC.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The association between OSA and baseline inflammatory biomarkers, peripheral lymphocytes classification and count.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The Spearman correlation test will be used to identify the association between sleep monitor results and the baseline inflammatory biomarkers, peripheral lymphocytes classification and count, including AHI, ODI, lowest SpO2, SpO2<90%, OAI, CAI, the longest apnea duration
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Compared the baseline gut microbiome between Group NSCLC and Group OSA+NSCLC.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Record baseline gut microbiome by metagenomic shotgun sequencing, then compare between Group NSCLC and Group OSA+NSCLC.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The association between OSA and the diversity of gut microbiome.
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The Spearman correlation test will be used to identify the association between sleep monitor results and the diversity of gut microbiome, including AHI, ODI, lowest SpO2, SpO2<90%, OAI, CAI, the longest apnea duration.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Investigators

  • Study Chair: Jing Ma, MD, Peking University First Hospital
  • Study Director: Guangfa Wang, MD, Peking University First Hospital
  • Study Director: Yuan Cheng, Peking University First Hospital
  • Study Director: Ligong Nie, Peking University First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2021

Primary Completion (Anticipated)

December 31, 2025

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

January 30, 2021

First Submitted That Met QC Criteria

February 4, 2021

First Posted (Actual)

February 8, 2021

Study Record Updates

Last Update Posted (Actual)

April 26, 2022

Last Update Submitted That Met QC Criteria

April 24, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-405

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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