NCT04355806

Brief Summary

This project is to assess the immunogenicity, safety and overall survival impact of intramuscular injection of trivalent influenza vaccine in non-small cell lung cancer (NSCLC) patients with PD-1/PD-L1 inhibitor treatment.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
160

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2020

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 9, 2020

Completed
12 days until next milestone

First Posted

Study publicly available on registry

April 21, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

June 1, 2020

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2023

Completed
Last Updated

April 21, 2020

Status Verified

April 1, 2020

Enrollment Period

2.6 years

First QC Date

April 9, 2020

Last Update Submit

April 20, 2020

Conditions

Non Small Cell Lung CancerInfluenza Vaccine

Keywords

Non-Small Cell Lung CancerInfluenza VaccinePD-1 ReceptorProgrammed Cell Death 1 Ligand 1

Outcome Measures

Primary Outcomes (34)

  • Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)

    The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).

    Day 0 after vaccination

  • Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)

    The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).

    Day 2 after vaccination

  • Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)

    The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).

    Day 7 after vaccination

  • Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)

    The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).

    Day 21 after vaccination

  • Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)

    The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).

    Day 30 after vaccination

  • Titer of neutralization antibody

    Titer of neutralization antibody is measured by neutralization test.

    Day 0 after vaccination

  • Titer of neutralization antibody

    Titer of neutralization antibody is measured by neutralization test.

    Day 21 after vaccination

  • Titer of neutralization antibody

    Titer of neutralization antibody is measured by neutralization test.

    Day 30 after vaccination

  • Titer of neutralization antibody

    Titer of neutralization antibody is measured by neutralization test.

    Day 60 after vaccination

  • Titer of neutralization antibody

    Titer of neutralization antibody is measured by neutralization test.

    Month 6 after vaccination

  • Multiple chemokine and cytokine levels in peripheral blood

    IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.

    Day 0 after vaccination

  • Multiple chemokine and cytokine levels in peripheral blood

    IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.

    12 hours after vaccination

  • Multiple chemokine and cytokine levels in peripheral blood

    IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.

    Day 1 after vaccination

  • Multiple chemokine and cytokine levels in peripheral blood

    IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.

    Day 2 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 0 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    12 hours after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 1 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 2 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 7 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 21 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 30 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Day 60 after vaccination

  • The numbers and proportions of T lymphocyte subpopulations in peripheral blood

    The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.

    Month 6 after vaccination

  • Peripheral T cell activation and proliferation

    The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.

    Day 0 after vaccination

  • Peripheral T cell activation and proliferation

    The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.

    Day 30 after vaccination

  • Peripheral T cell activation and proliferation

    The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.

    Day 60 after vaccination

  • Peripheral T cell activation and proliferation

    The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.

    Month 6 after vaccination

  • Antibody-dependent cellular cytotoxicity (ADCC)

    The ADCC activities of NK-92 cells cultured by the sera from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.

    Day 0 after vaccination

  • Antibody-dependent cellular cytotoxicity (ADCC)

    The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.

    Day 30 after vaccination

  • Antibody-dependent cellular cytotoxicity (ADCC)

    The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.

    Day 60 after vaccination

  • Antibody-dependent cellular cytotoxicity (ADCC)

    The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.

    Month 6 after vaccination

  • Immune-related adverse events (irAEs)

    The performances and the grades of irAEs according to Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0) and their correlation with vaccination.

    June 2020- June 2023

  • Progression-free Survival (PFS)

    PFS is calculated as the time from from PD-1/PD-L1 inhibitor starting to the disease progression or the death from any cause.

    June 2020- June 2023 (3 year)

  • Overall Survival (OS)

    OS is calculated as the time from PD-1/PD-L1 inhibitor starting to the death from any cause.

    June 2020- June 2023 (3 year)

Secondary Outcomes (3)

  • Objective Response Rate (ORR)

    June 2020- June 2023 (3 year)

  • Disease Control Rate (DCR)

    June 2020- June 2023 (3 year)

  • Time to Treatment Failure (TFF)

    June 2020- June 2023 (3 year)

Study Arms (3)

Vaccinated NSCLC group

This group contains 100 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).

Drug: PD-1/PD-L1 inhibitorsBiological: Inactivated trivalent influenza vaccine

Vaccinated Health group

This group contains 30 healthy participants without immunosuppressive diseases, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).

Biological: Inactivated trivalent influenza vaccine

Unvaccinated NSCLC group

This group contains 30 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months without intramuscular injection of any inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).

Drug: PD-1/PD-L1 inhibitors

Interventions

PD-1/PD-L1 inhibitorsDRUG

Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al.

Also known as: PD-1/PD-L1 blockades, PD-1 monoclonal antibodies, PD-L1 monoclonal antibodies
Unvaccinated NSCLC groupVaccinated NSCLC group
Inactivated trivalent influenza vaccineBIOLOGICAL

Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane.

Also known as: Flu Vaccines, Influenza Virus Vaccines, Influenza Vaccine, Trivalent, Vaccine, Trivalent Influenza, Flu Shot
Vaccinated Health groupVaccinated NSCLC group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

NSCLC patients receiving PD-1/PD-L1 inhibitors during this project

You may qualify if:

  • NSCLC patients were diagnosed with clear pathological classification and receive PD-1 / PD-L1 inhibitor treatment during this project.
  • NSCLC patients have the exact start and end time of PD-1 / PD-L1 inhibitor and / or the vaccination time and follow-up information.
  • The healthy participants are not in an immunosuppressive state, such as cancer, HIV, autoimmune diseases, and long-term use of immunosuppressive drugs.
  • The healthy participants have exact vaccination time.
  • All participants have complete clinical and laboratory diagnostic data.
  • All participants are 18-75 years, regardless of gender.
  • All participants have agreed and signed the consent form before enrollment.

You may not qualify if:

  • Patients with unclear diagnosis of lung cancer were excluded.
  • Patients with incomplete clinical data or incomplete follow-up records.
  • Patients without signed informed consent.
  • Patient has received blood transfusion within three months.
  • Patients with HIV, Hepatitis B and Hepatitis C infections.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong

Hong Kong, Hong Kong, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biospecimen includes the peripheral blood samples collected on day0, 12h, day1, 2, 7, 21, 30, 60 and 6 months after vaccination.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungInfluenza, Human

Interventions

Immune Checkpoint InhibitorsInfluenza Vaccines

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesRespiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesAntineoplastic Agents, ImmunologicalAntineoplastic AgentsTherapeutic UsesViral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Yayi He, PhD, MD

    Shanghai Pulmonary Hospital, Shanghai, China

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yayi He

CONTACT

86138188286232250601@qq.com

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

April 9, 2020

First Posted

April 21, 2020

Study Start

June 1, 2020

Primary Completion

December 31, 2022

Study Completion

May 31, 2023

Last Updated

April 21, 2020

Record last verified: 2020-04

Locations

CN(2)