UMIN-ICDS Clinical Trial

Public title

Progression-free, disease-free, and recurrence-free survivals as surrogate in melanoma perioperative immune checkpoint inhibitor trials.

Acronym

Progression-free, disease-free, and recurrence-free survivals as surrogate in melanoma perioperative immune checkpoint inhibitor trials.

Scientific Title

Progression-free, disease-free, and recurrence-free survivals as surrogate in melanoma perioperative immune checkpoint inhibitor trials.

Scientific Title:Acronym

Progression-free, disease-free, and recurrence-free survivals as surrogate in melanoma perioperative immune checkpoint inhibitor trials.

Region

Japan

Condition

Malignant melanoma

Classification by specialty

Dermatology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Clinical studies have been conducted to evaluate the effectiveness and safety of peri-operative ICI. The most desirable clinical endpoint is overall survival (OS), which provides a direct benefit to patients with melanoma without evaluation bias. Regulatory views OS as the gold standard outcomes in studies for solid malignancies. Nonetheless, in contrast to patients with advanced solid tumor who cannot undergo surgery, those receiving surgery aiming complete cure have a longer life expectancy and lower death risk. Identifying significant differences in mortality between groups demands a lengthy observation and a larger number of subjects. Hence, alternative measures like progression-free survival (PFS), disease-free survival (DFS), and recurrence-free survival (RFS) are frequently chosen as the main outcomes. The introduction of immune checkpoint inhibitors (ICI) as part of the perioperative regimen has also improved the patient survival. This advancement has made it more difficult to demonstrate substantial differences in OS, thereby researchers are motivated to select alternative endpoints. A critical concern with employing these surrogate outcomes in trials of perioperative ICI is the limited treatment choices after the cancer recurrence. For instance, if DFS is the same, those not receiving perioperative ICI have a broader regimen option, which might result in a longer OS.
The aim of this systematic review is to evaluate whether PFS, DFS, and RFS reasonably reflect OS in trials involving perioperative ICI for melanoma.

Basic objectives2

Others

Basic objectives -Others

The aim of this systematic review is to evaluate whether PFS, DFS, and RFS reasonably reflect OS in trials involving perioperative ICI for melanoma.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The study-level outcomes of our concern will be the hazard ratios (HRs) of event-free survival (EFS, HRefs) and HR of OS (HRos). EFS includes PFS, DFS, and RFS.
We will assess the Spearman's rank correlation between HRefs and HRos.

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
Eligible articles will be English report on randomized controlled trials (RCTs). Inclusion of conference abstracts will be permissible for this analysis. The phase of the study will not serve as a criterion for exclusion.

Patient selection
Patient with cutaneous malignant melanoma will be the target population, without regard to the stage of cancer, histopathological type, or specific genetic mutation, provided these patients are identified as suitable for perioperative chemotherapy by the original study's authors.

Treatment
Concerned treatment is the perioperative ICI, including pre-operative (neo-adjuvant) and post-operative (adjuvant) therapies, regardless of the ICI type, drug dose, and regimens. Co-administration of cytotoxic agents and molecular targeted therapy will be acceptable.

Key exclusion criteria

Perioperative ICI combined with radiological treatment will be excluded.

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

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

2024

Year

04

Month

04

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

2024

Year

04

Month

04

Day

Date of IRB

Anticipated trial start date

2024

Year

04

Month

04

Day

Last follow-up date

2025

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Subgroup Analysis
The planed subgroup analyses focusing on DFS, RFS, PFS, adjuvant therapy, neoadjuvant therapy, and phase III trials.

Statistical Analysis
The weighted Spearman's rank correlation coefficient (r) will be applied for evaluating how HR for surrogate endpoints (HRefs) reflects HR of overall survival (HRos). The interpretation of the coefficient is as follows: no correlation is indicated by |r| < 0.2; a weak correlation by 0.2 < |r| < 0.4; a moderate correlation by 0.4 < |r| < 0.6; a strong correlation by 0.6 < |r| < 0.8; and an excellent correlation by 0.8 < |r|. The analysis will first assess the correlation using the initial data set, followed by an adjustment for reciprocal duplication. The weighting for each study in the analysis will be based on the reciprocal of the variance of the natural logarithm of HRos. The correlation calculation will be conducted using the "corr" function in the "boot" package in R software. To create the graphical representations, GraphPad Prism software version 9.2.0 (GraphPad Software, San Diego, CA, USA) will be utilized. P value is calculated for unweighted Spearman's rank correlation.

Registered date

2024

Year

04

Month

03

Day

Last modified on

2024

Year

04

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000061708