UMIN-ICDS Clinical Trial

Public title

Progression-free, disease-free, and recurrence-free survivals as surrogate in NSCLC perioperative chemotherapy trials

Acronym

Progression-free, disease-free, and recurrence-free survivals as surrogate in NSCLC perioperative chemotherapy trials

Scientific Title

Progression-free, disease-free, and recurrence-free survivals as surrogate in NSCLC perioperative chemotherapy trials

Scientific Title:Acronym

Progression-free, disease-free, and recurrence-free survivals as surrogate in NSCLC perioperative chemotherapy trials

Region

Japan

Condition

NSCLC

Classification by specialty

Pneumology

Chest surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Clinical trials have been designed to assess the efficacy and safety of perioperative chemotherapy. The ideal efficacy endpoint is overall survival (OS), as it offers a straightforward, unbiased metric representing patient benefit. Both the U.S. Food and Drug Administration and the European Medicines Agency regard OS as the most reliable endpoint in regulatory evaluations concerning NSCLC chemotherapy. However, unlike patients with advanced lung cancer ineligible for surgery, those undergoing curative-intent surgery have longer life expectancies and a lower incidence of death events. To detect statistical significance in mortality between groups, studies require a long observation period and/or a large patient accrual, making study design challenging. Therefore, surrogate endpoints such as progression-free survival (PFS), disease-free survival (DFS), and recurrence-free survival (RFS) are often selected for the primary outcome of a trial. Recently, immune checkpoint inhibitors (ICI) used as perioperative chemotherapy regimens have been shown to extend patient survival. Consequently, confirming significant differences in OS has become more difficult, making these surrogates increasingly attractive. A fundamental issue in using surrogate endpoints in the perioperative chemotherapy trial is ignoring the limited treatment options available upon recurrence. For example, if DFS is equivalent, patients in the non-perioperative chemotherapy group have a wider array of chemotherapy choices and are expected to have longer OS.
The aim of this systematic review is to assess whether surrogate endpoints are a reasonable in trials involving perioperative chemotherapy for NSCLC.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The primary endpoints consist of the correlation between hazard ratios (HRs) of surrogate endpoints and overall survival (OS). The surrogates, namely DFS, RFS, and PFS, will be evaluated collectively for the primary endpoints. DFS, RFS, and PFS will be assessed specifically as part of the subgroup analysis.

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//
Any article written in English language presenting a randomized controlled trial (RCT)is considered eligible. Conference abstracts will be accepted for this study. The study phase is not a factor for exclusion.

Patients//
Patients with NSCLC will be evaluated, irrespective of cancer stage, pathological subtype, or driver mutation, as long as the patients were candidates for perioperative chemotherapy according to the authors of the original article.

Treatment//
This study is focused on perioperative chemotherapy, including NAC and AC, regardless of the agents, regimens, and number of cycles used. Cytotoxic agents, molecular targeted therapy (MTT), immune checkpoint inhibitors (ICI), or combinations thereof are acceptable. Any treatment combined with radiotherapy will not be included.

Key exclusion criteria

Not specified

Target sample size

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

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Name of contact person

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

045-787-2800

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Institute

Yokohama City University Hospital

Institute

Department

Personal name

Organization

Yokohama City University Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Yokohama City University Hospital

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

Tel

045-787-2800

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

2023

Year

10

Month

20

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2023

Year

10

Month

10

Day

Date of IRB

Anticipated trial start date

2023

Year

10

Month

10

Day

Last follow-up date

2024

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Study Search
We will perform a comprehensive systematic database search in the following databases: PubMed, the Cochrane CENTRAL, EMBASE, and Web of Science.

Subgroup Analysis
We plan to conduct subgroup analyses focusing on the following factors: DFS, RFS, PFS, NAC, AC, MTT, ICI, and phase III trials.

Statistics
We assess surrogacy using the weighted Spearman's rank correlation coefficient (r) between HRos and HRsurrogates. The coefficient is interpreted as follows: no correlation, |r| < 0.2; weak correlation, 0.2 < |r| < 0.4; moderate correlation, 0.4 < |r| < 0.6; strong correlation, 0.6 < |r| < 0.8; or excellent correlation, 0.8 < |r|. The correlation was assessed for original data, and then the correlation after reciprocal duplication will be calculated to avoid underestimation of r. The weight assigned to each study was determined by the reciprocal of the squared standard error (SE) of log HRos. The "corr" command within the "boot" package in the R software will be applied. GraphPad Prism version 9.2.0 (GraphPad Software, San Diego, CA, USA) is used to generate figures.

Registered date

2023

Year

10

Month

20

Day

Last modified on

2023

Year

10

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000059968