UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000042164
Receipt number	R000048130
Scientific Title	Network meta-analysis for chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration
Date of disclosure of the study information	2020/10/20
Last modified on	2021/12/20 12:50:12

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Basic information

Public title

Network meta-analysis for chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration

Acronym

Network meta-analysis for chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration

Scientific Title

Network meta-analysis for chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration

Scientific Title:Acronym

Network meta-analysis for chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration

Region

Japan

Condition

chemo-naive incurable not highly PD-L1-expressed non-squamous non-small cell lung cancer without confirmed driver alteration

Classification by specialty

Medicine in general

Classification by malignancy

Malignancy

Genomic information

Objectives

Narrative objectives1

Several regimens combining ICI, bevacizumab, and cytotoxic drugs are recommended even for a patient with low or negative PD-L1 score since they greatly improved objective response rate (ORR), progression-free survival (PFS), and even overall survival (OS) of patients with low-/negative-PD-L1 expressed NSCLC without substantially increasing a risk of adverse event compared to reference platinum regimens without ICI. However, few RCTs have directly compared ICI regimens because such a trial demands a large number of subjects to reveal small outcome difference. Nonetheless, oncologists still earn to know rank order regarding efficacy and safety endpoints among ICI regimens because it is key to select treatment for a real patient. A network-meta-analysis is the best analytical technique to enable indirect comparison among numerous regimens. Our previous network meta-analysis published in 2017 evaluated only non-ICI non-kinase-inhibitor regimens for chemo-naive incurable NSCLC. Aim of the current study, focusing on ICI regimens and negative- or low-PD-L1 expressed non-squamous NSCLC cases without driver alteration, is to update the previous network meta-analysis.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Assessment

Primary outcomes

The primary outcome of this analysis is overall survival (OS) evaluated with hazard ratio (HR, HRos).

Key secondary outcomes

The secondary endpoints are HR for progression-free survival (PFS, HRpfs), odds ratio (OR) of objective response rate (ORrr), OR of adverse event with Common Terminology Criteria for Adverse Events grade III or higher (ORae) , and OR of treatment related death (ORtrd). Disease progression and objective RR should be assessed in compliance with the Response Evaluation Criteria In the Solid Tumors guidelines published in 2000 or its 2009 revision. Imaging evaluation that was done by the blinded independent central reviewing is preferred, if available. The first adverse event with grade III or higher will be counted even if a patient experienced adverse event twice or more.

Base

Study type

Others,meta-analysis etc

Study design

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Intervention

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

English-written individually randomized controlled trials for incurable NSCLC are collected. Studies focusing on patients with a driver mutation or translocation will be excluded. A conference abstract is allowed only for ICI-related treatment because we are keen to such a trial.
Eligible treatments are first-line chemotherapy including cytotoxic agents, molecular targeted therapies, and immune checkpoint inhibitors. Platinum doublet counterpart had to be one of the following third-generation chemotherapy agents: Vinorelbine (Vnr), Docetaxel (Dtx), Paclitaxel (Ptx), nanoparticle albumin-bound Ptx (nabPtx), Irinotecan (Cpt11), Gemcitabine (Gem), Pemetrexed (Pemt), and Tegafur gimeracil oteracil (S1). Adding Bev on platinum regimen is accepted.
Non-squamous NSCLC patients with advanced, locally advanced, or recurrent disease were included. A study focusing on patients with poor performance status or elderly should be excluded.

Key exclusion criteria

Kinase inhibitors targeting EGFR, ALK, ROS1, and BRAF are beyond our concern.
A patient whose PD-L1 protein expression determined by tumor proportion score (TPS) is 50% or higher will be excluded because current guidelines recommends treatment option differently for those with TPS <50% and >=50%. If subset of study population fit our criteria, the data of the subset will be analyzed. For example, a study separately provide data of three populations whose TPS score is 0%, 1-49%, and 50-%, we will collect data of populations with TPS of 0% and 1-49%. Tumor mutation burden is not questioned.
If a study focusses on patients with squamous NSCLC, driver alteration, or TPS of 50% or higher, the study should be excluded. However, a study without criteria regarding pathological subclassification of NSCLC, driver gene, and TPS is acceptable, otherwise most NSCLC studies will be excluded.

Target sample size

Research contact person

Name of lead principal investigator

1st name Nobuyuki

Middle name

Last name Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, fukuura, Kanazawa, Yokohama, Japan

TEL

+81457872700

Email

horitano@yokohama-cu.ac.jp

Public contact

Name of contact person

1st name Nobuyuki

Middle name city

Last name Horita

Organization

Yokohama City University University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, fukuura, Kanazawa, Yokohama, Japan

TEL

+81457872700

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Sponsor or person

Institute

Yokohama City University University Hospital

Institute

Department

Personal name

Funding Source

Organization

Yokohama City University University Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Other related organizations

Co-sponsor

Name of secondary funder(s)

IRB Contact (For public release)

Organization

Yokohama City University University Hospital

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

Tel

+81457872700

Email

horitano@yokohama-cu.ac.jp

Secondary IDs

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Other administrative information

Date of disclosure of the study information

2020 Year 10 Month 20 Day

Related information

URL releasing protocol

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000048130

Publication of results

Published

Result

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/34791815/