UMIN-CTR Clinical Trial

Public title

Correlation with overall survival of response rate (RR) and disease control rate (DCR) in phase II randomized controlled trials evaluating second- or later-line chemotherapy for advanced, locally advanced, and recurrent non-small cell lung cancer.

Acronym

Correlation with overall survival of response rate (RR) and disease control rate (DCR) in phase II randomized controlled trials evaluating second- or later-line chemotherapy for advanced, locally advanced, and recurrent non-small cell lung cancer.

Scientific Title

Correlation with overall survival of response rate (RR) and disease control rate (DCR) in phase II randomized controlled trials evaluating second- or later-line chemotherapy for advanced, locally advanced, and recurrent non-small cell lung cancer.

Scientific Title:Acronym

Correlation with overall survival of response rate (RR) and disease control rate (DCR) in phase II randomized controlled trials evaluating second- or later-line chemotherapy for advanced, locally advanced, and recurrent non-small cell lung cancer.

Region

Japan

Condition

NSCLC

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Although objective response rate (ORR) and disease control rate (DCR) are frequently used as primary endpoints of phase II randomized non-small cell lung cancer (NSCLC)trials that evaluate second- or later-line chemotherapy, how ORR and DCR reflect overall survival (OS) in the phase II trial have not been sufficiently assessed. We are quite unsure whether ORR and DCR correctly associate with the OS in NSCLC phase II trials evaluating second- or later-line chemotherapy. ORR and DCR seem unreliable due to a low ORR, a poor DCR, and small number of evaluated patients in phase II trials for cases after first-line relapse.
In this study, we evaluate how trial-level ORR and DCR correlate with OS in the phase II randomized NSCLC trials that evaluate second- or later-line chemotherapy.

Basic objectives2

Others

Basic objectives -Others

Although objective response rate (ORR) and disease control rate (DCR) are frequently used as primary endpoints of phase II randomized non-small cell lung cancer (NSCLC)trials that evaluate second- or later-line chemotherapy, how ORR and DCR reflect overall survival (OS) in the phase II trial have not been sufficiently assessed. We are quite unsure whether ORR and DCR correctly associate with the OS in NSCLC phase II trials evaluating second- or later-line chemotherapy. ORR and DCR seem unreliable due to a low ORR, a poor DCR, and small number of evaluated patients in phase II trials for cases after first-line relapse.
In this study, we evaluate how trial-level ORR and DCR correlate with OS in the phase II randomized NSCLC trials that evaluate second- or later-line chemotherapy.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Correlation with hazard ratio (HR) for OS (HRos) of odds ratio of RR (ORrr), odds ratio of DCR(ORdcr), difference of RR (d-RR, %), and difference of DCR (d-RCR, %) were assessed. Response, stable disease, and disease progression had to be evaluated without considerable deviation from the Response Evaluation Criteria in Solid Tumors (RECIST) 2000 guidelines and the RECIST 2009 revised guidelines.

Key secondary outcomes

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Study Selection: study design
We will include phase II RCTs that evaluate second- or later-line chemotherapy for advanced, locally advanced, and recurrent NSCLC. Articles need to be written up as full articles, brief reports, or conference abstracts regardless of their primary end point. Non-English language reports will be excluded. A phase I/II trial will be allowed. A phase II/III trial will be included when data from phase II part can be extractable

Study selection: treatment
The interventions include cytotoxic agents, molecular targeted therapies, immune checkpoint inhibitors, and their combinations. Immunotherapy other than immune checkpoint inhibitors will not be included because such treatment is not current standard. Comparison of the same drugs in the form of low-dose versus high-dose or weekly versus 3-weekly regimens will be allowed. Maintenance therapy after the first-line chemotherapy will not considered as the second-line treatment.

Key exclusion criteria

Study Selection: study design
We will include phase II RCTs that evaluate second- or later-line chemotherapy for advanced, locally advanced, and recurrent NSCLC. Articles need to be written up as full articles, brief reports, or conference abstracts regardless of their primary end point. Non-English language reports will be excluded. A phase I/II trial will be allowed. A phase II/III trial will be included when data from phase II part can be extractable

Study selection: treatment
The interventions include cytotoxic agents, molecular targeted therapies, immune checkpoint inhibitors, and their combinations. Immunotherapy other than immune checkpoint inhibitors will not be included because such treatment is not current standard. Comparison of the same drugs in the form of low-dose versus high-dose or weekly versus 3-weekly regimens will be allowed. Maintenance therapy after the first-line chemotherapy will not considered as the second-line treatment.

Target sample size

Name of lead principal investigator

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University

Division name

Department of Pulmonology

Zip code

236-0004

Address

3-9, Fukuura, Kanazawa, Yokohama

TEL

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Name of contact person

1st name	Nobuyuki
Middle name
Last name	Horiat

Organization

Yokohama City University

Division name

Department of Pulmonology

Zip code

236-0004

Address

3-9, Fukuura, Kanazawa, Yokohama

TEL

045-787-2800

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Institute

Yokohama City University

Institute

Department

Personal name

Organization

Yokohama City University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Yokohama City University

Address

3-9, Fukuura, Kanazawa, Yokohama

Tel

0457872800

Email

horitano@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

05

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

9059

Results

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Results date posted

2021

Year

12

Month

20

Day

Results Delayed

Results Delay Reason

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Date of the first journal publication of results

Baseline Characteristics

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Participant flow

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Adverse events

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Outcome measures

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Plan to share IPD

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

IPD sharing Plan description

Please see:
Transl Lung Cancer Res. 2021 May;10(5):2278-2289. doi: 10.21037/tlcr-20-1120.

Recruitment status

Main results already published

Date of protocol fixation

2020

Year

05

Month

15

Day

Date of IRB

2020

Year

05

Month

15

Day

Anticipated trial start date

2020

Year

05

Month

15

Day

Last follow-up date

2021

Year

05

Month

15

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study will be conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Study Search
We will systematically search PubMed, the Cochrane database, EMBASE, and Web of Science as of May 15, 2020. The search formula for PubMed is the followings: (Non Small Cell Lung Cancer OR Non Small Cell Lung Carcinoma OR NSCLC OR Adenocarcinoma of Lung OR Squamous carcinoma of lung) AND (Recurrent OR Recurrence OR relapsed OR Advanced OR Advance OR Metastatic OR Metastasis OR Stage IV OR Stage III OR Stage four OR Stage three) AND (Phase II OR Phase two OR Phase 2) AND (Randomized OR Randomised OR Randomly OR RCT) AND (2nd line OR Second line OR 3rd line OR Third line OR later line). Reference lists in the included articles were also checked as hand search.

Assessment of Risk for Bias in Included Studies
Risk for bias in individual RCTs will be evaluated using the Cochrane risk of bias table.


Data Extraction
Data will be extracted by the two investigators independently and cross-checked.
We prefer OS data obtained on the basis of predeclared timing of each original trial.
The first arm and the second arm of each RCT will be decided according to the description in each article. If an article randomized patients into three or more arms, the two arms with the largest number of patients were extracted. ORR and DCR will be preferably determined by full-analysis set or intention-to-treat policy; thus, a denominator includes not-evaluable patients.
If necessary, we adopt Parmar's method to extract data from Kaplan-Meier curves [PMID: 9921604]

Data Synthesis and Interpretation
Spearman's rank correlation will be calculated using GraphPad PRISM ver 7.02 (San Diego, CA, USA). When one or more cells in the two by two contingency to calculate ORR and DCR were null, 0.5 was added.

Registered date

2020

Year

05

Month

15

Day

Last modified on

2021

Year

12

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046117