UMIN-CTR Clinical Trial

Basic information
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
Condition	NSCLC
Classification by specialty	Pneumology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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

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	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

Research contact person
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

Public contact
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

Sponsor
Institute	Yokohama City University
Institute
Department

Funding Source
Organization	Yokohama City University
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Yokohama City University
Address	3-9, Fukuura, Kanazawa, Yokohama
Tel	0457872800
Email	horitano@yokohama-cu.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 05 Month 15 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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.

Progress
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

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.

Management information
Registered date	2020 Year 05 Month 15 Day
Last modified on	2021 Year 12 Month 20 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046117