UMIN-CTR Clinical Trial

Public title

Pegfilgrastim subcutaneous injection 3.6mg Drug use results survey
-Prevention of chemotherapy-induced febrile neutropenia-

Acronym

Pegfilgrastim subcutaneous injection 3.6mg Drug use results survey
-Prevention of chemotherapy-induced febrile neutropenia-

Scientific Title

Pegfilgrastim subcutaneous injection 3.6mg Drug use results survey
-Prevention of chemotherapy-induced febrile neutropenia-

Scientific Title:Acronym

Pegfilgrastim subcutaneous injection 3.6mg Drug use results survey
-Prevention of chemotherapy-induced febrile neutropenia-

Region

Japan

Condition

Patients who received pegfilgrastim for the first time to prevent of chemotherapy-induced febrile neutropenia

Classification by specialty

Gastroenterology	Hepato-biliary-pancreatic medicine	Pneumology
Hematology and clinical oncology	Nephrology	Obstetrics and Gynecology
Pediatrics	Dermatology	Urology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The objective of this survey was to confirm the safety and efficacy of peg-filgrastim administered to prevent FN after cancer chemotherapy in a real world clinical practice setting.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Consider the following safety issues
-Side effects/infectious diseases (types, incidence, etc.)
-Factors that may affect safety
-Serious adverse events
-Safety specifications

Consider the following effectiveness issues
-Febrile neutropenia
-Changes in neutrophil count
-Examination of factors thought to influence changes in neutrophil count and the onset of febrile neutropenia

Key secondary outcomes

Study type

Observational

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

Patients who received pegfilgrastim for the first time to prevent of chemotherapy-induced febrile neutropenia

Key exclusion criteria

-If a contract with the facility has not been concluded
-If the start date of Pegfilgrastim administration is outside the contract period
-If there are duplicate registered cases (already registered)
-If the number of registrations exceeds the number of contracted cases
-If the case is registered after Pegfilgrastim administration
-If registered by a doctor other than the contracted doctor

Target sample size

1500

Name of lead principal investigator

1st name	Nobuhiro
Middle name
Last name	Shibata

Organization

Kansai Medical University Hospital

Division name

Cancer Treatment Center

Zip code

573-1191

Address

3-1 Shinmachi 2 Chome, Hirakata City, Osaka, Japan

TEL

+81(0)72-804-0101

Email

shibanob@hirakata.kmu.ac.jp

Name of contact person

1st name	Hiroshi
Middle name
Last name	Kuwazawa

Organization

Kyowa Kirin Co., Ltd.

Division name

Pharmacovigilance Division

Zip code

100-0004

Address

Otemachi Financial City Grand Cube 1-9-2 Otemachi, Chiyoda-ku, Tokyo

TEL

07031439628

Homepage URL

Email

hiroshi.kuwazawa.wd@kyowakirin.com

Institute

Kyowa Kirin Co., Ltd.

Institute

Department

Personal name

Hiroshi Kuwazawa

Organization

Kyowa Kirin Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Research Ethical Review Committee of Kyowa Kirin Co., Ltd.

Address

Otemachi Financial City Grand Cube 1-9-2 Otemachi, Chiyoda-ku, Tokyo

Tel

03-5205-7202

Email

researchethics.fj@kyowakirin.com

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

27

Day

URL releasing protocol

https://www.pmda.go.jp/drugs_reexam/2023/P20231226001/index.html

Publication of results

Unpublished

URL related to results and publications

https://www.pmda.go.jp/drugs_reexam/2023/P20231226001/index.html

Number of participants that the trial has enrolled

1531

Results

1531 patients were included in the safety and 1523 were included in the efficacy analysis set.ADRs were 18.88%, and the main ADRs were "back pain" 3.59%, "fever" 3.14%, "arthralgia" 2.16%, "Hepatic functional abnormality" 1.50%, "muscle pain" 1.31%, and "bone pain" 1.18%.FN due to cancer chemotherapy after administration of pegfilgrastim can be suppressed in both "primary preventive administration" and "secondary preventive administration" from cycle 1 (first administration of pegfilgrastim).

Results date posted

2024

Year

04

Month

26

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The patient backgrounds of the 1531 patients included in the safety analysis set were shown in below.
The main diseases were breast cancer in 52.25% (800/1531 patients), NHL in 25.21% (386/1531 patients), and lung cancer in 11.03% (169/1531 patients) [NSCLC 5.94% (91 /1531 patients), SCLC 5.09% (78/1531 patients)].
Regarding gender, 29.92% (458/1531 patients) were male and 70.08% (1073/1531 patients) were female.
The mean age (standard deviation) at the start of pegfilgrastim administration was 60.9 years (13.1 years), with 0-14 years (children) at 0.07% (1 /1531 patients) and 15-64 years at 53.49% (819/1531 patients). 46.44% (711 /1531 patients) were aged 65 years or older (elderly).
Most treatments were performed on an outpatient basis, accounting for (62.83% (962/1531 patients)), and most of the performance status (PS) was 0, 69.11% (1058/1531 patients).
The main cancer chemotherapy regimens for 800 patients of breast cancer were FEC therapy in 28.00% (224/800 patients), TC therapy in 27.50% (220/800 patients), and EC therapy in 18.00% (144/800 patients).
The main cancer chemotherapy regimens for 386 patients of NHL were R-CHOP therapy in 38.60% (149/386 patients) and CHOP therapy in 11.66% (45/386 patients).
The main cancer chemotherapy regimens for 91 patients of lung cancer (NSCLC) were DTX single therapy in 23.08% (21/91 patients), DTX/RAM therapy in 12.09% (11/91 patients), and CBDCA/PEM/BV therapy in 10.99% (10/91 patients), and Lung cancer (SCLC) were 78 patients, CBDCA/VP-16 therapy in 38.46% (30/78 patients), AMR monotherapy in 29.49% (23/78 patients) and CDDP/VP-16 therapy in 19.23% (15/78 patients).

Participant flow

Pegfilgrastim was administered almost according to the package insert for all cycles.
The average time to start administration of pegfilgrastim in each cycle of up to 6 cycles was 3.4 to 4.0 days from the start date of cancer chemotherapy (day 1).
Furthermore, the average number of days from administration of pegfilgrastim to the start of the next cancer chemotherapy was 20.4 to 21.8 days, and the average number of days from the end of cancer chemotherapy to administration of pegfilgrastim was 2.0 to 2.2 days.

Adverse events

In the safety analysis set, 18.88% (289/1531 patients) had ADRs, 3.27% (50/1531 patients) had serious ADRs, and 0.07% (1/1531 patients) had ADRs reported with fatal outcome, but there was no reasonable possibility of a causal relationship indicated between the event and pegfilgrastim.
During this survey, ADRs unexpected from "Precautions" (unexpected ADRs) were collected from 69 patients. Unexpected ADRs experienced by at least 0.20% (3 patients) were as follows: "Febrile neutropenia"in 0.78% (12/1531 patients) "Neuropathy peripheral" and "Blast cell count increased" in 0.26% (4/1531 patients) each and"Cystitis" "Renal impairment" and "Platelet count increased"in 0.20% (3/1531 patients) each.
Furthermore, based on results from this survey, the necessity of additional risk minimization activities was examined for the priority survey items and the safety specifications (including adverse events other than safety specifications): "interstitial lung disease" "splenomegaly and/or splenic rupture" "anaphylactic shock" "acute respiratory distress syndrome" "blast cell count increased""capillary leak syndrome" "events relating to bone pain/back pain/etc" "Sweet's syndrome" "cutaneous vasculitis" "febrile neutropenia" "thrombocytopenia" "secondary malignancy" "large-vessel vasculitis" and "antibody expression." After evaluating the current risk minimization activities, the company determines that no additional measures are currently required.

Outcome measures

Among patients whose indication for use of pegfilgrastim (company`s assessment) was "primary prophylactic administration," febrile neutropenia was observed in 13.85% of patients (18 /130 patients) who received chemotherapy (including regimens different from those administered with pegfilgrastim) within the last 3 months before the first dose of pegfilgrastim, whereas the overall incidence of febrile neutropenia after pegfilgrastim administration was 5.67% (44 /776 patients). Among patients whose indication for use of pegfilgrastim (company`s assessment) was "secondary prophylactic administration," febrile neutropenia was observed in 40.29% of patients (301 /747 patients) who received chemotherapy (including regimens different from those administered with pegfilgrastim) within the last 3 months before the first dose of pegfilgrastim, whereas the overall incidence of febrile neutropenia after pegfilgrastim administration was 4.28% (32 /747 patients).

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

06

Month

10

Day

Date of IRB

2021

Year

06

Month

30

Day

Anticipated trial start date

2015

Year

08

Month

26

Day

Last follow-up date

2017

Year

11

Month

10

Day

Date of closure to data entry

Date trial data considered complete

2019

Year

12

Month

17

Day

Date analysis concluded

Other related information

Drug use results survey based on the ministerial ordinance on implementation of Good Post-marketing Study Practice

Registered date

2024

Year

04

Month

26

Day

Last modified on

2024

Year

05

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000061609