UMIN-CTR Clinical Trial

Public title

A phase II study of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations.

Acronym

A phase II study of gefitinib with TRT in patients with stage III NSCLC harboring EGFR mutations.

Scientific Title

A phase II study of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations.

Scientific Title:Acronym

A phase II study of gefitinib with TRT in patients with stage III NSCLC harboring EGFR mutations.

Region

Japan

Condition

Non-Small Cell Lung Cancer

Classification by specialty

Pneumology	Hematology and clinical oncology	Radiology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To explore the efficacy and the tolerability of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Progression free survival rate at 2 years.

Key secondary outcomes

Overall response rate, progression free survival rate at 1 year, progression free survival, survival rate at 1 year, survival rate at 2 years, overall survival, and safety.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

An oral dose of 250mg of gefitinib is administered daily beginning on day 1, with once-daily thoracic radiotherapy delivered at 2 Gy per day to a total dose of 64 Gy.

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

20

years-old

<=

Age-upper limit

75

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Pathologically confirmed NSCLC
2) Treatment naïve, unresectable stage III disease, whereas those with T3N1 desease, contralateral mediastinal lymph node metastasis, pulmonary metastasis, and atelectasis of the entire hemithorax were excluded
3) Harboring EGFR mutation (exon 19 deletion, and / or exon 21 L858R point mutation)
4) an age of 20-75 years
5) ECOG PS of 0 or 1
6)With evaluable target lesions as per RECIST ver. 1.1
7) With adequate organ function
8) Confirmed as eligible for the protocol defined radiotherapy by radiologists
9) Provided written informed consent

Key exclusion criteria

1) Harboring exon 20 T790M mutation.
2) Incapable of oral intake
3) With intestinal paralysis, or ileus
4) Chronic diarrhea
5)Exhibiting significant interstitial pneumonitis, or pulmonary fibrosis in the chest CT
6) Active infection
7) Positive for HBs antigen
8) Uncontrolled diabetes mellitus
9) Severe heart disease
10) Systemic treatment with steroids
11) Concomitant cancers within 5 years
12) Prior history of thoracic radiotherapy
13) History of sereous drug allegies
14) Pregnancy, breast feeding, or hesitation in contraception
15) Other conditions not suitable for this study

Target sample size

27

Name of lead principal investigator

1st name	Haruyasu
Middle name
Last name	Murakami

Organization

Shizuoka Cancer Center

Division name

Division of Thoracic Oncology

Zip code

411-8777

Address

1007, Shimonagakubo, Nagaizumi-cho, Shizuoka, Japan

TEL

055-989-5222

Email

ha.murakami@scchr.jp

Name of contact person

1st name	Shinichiro
Middle name
Last name	Nakamura

Organization

West Japan Oncology Group

Division name

WJOG datacenter

Zip code

411-8777

Address

Namba Plaza Bldg.304-1-5-7,Motomachi Naniwa-ku,Osaka 556-0016 JAPAN

TEL

06-6633-7400

Homepage URL

Email

datacenter@wjog.jp

Institute

West Japan Oncology Group

Institute

Department

Personal name

Organization

AstraZeneca K.K

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Shizuoka Cancer Center Certified Review Board

Address

1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka

Tel

055-989-5222

Email

rinsho_office@scchr.jp

Secondary IDs

YES

Study ID_1

jRCTs041180080

Org. issuing International ID_1

Ministry of Health, Labour and Welfare

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2012

Year

07

Month

06

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs041180080

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/34116229/

Number of participants that the trial has enrolled

28

Results

Among unresectable locally-advanced NSCLC patients with EGFR mutation, gefitinib with concurrent thoracic radiotherapy showed manageable safety profiles, but did not improve PFS rate at 2 years.

Results date posted

2023

Year

05

Month

17

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

A total of 28 patients were enrolled and 27 were eligible. Of those, median age was 67 (range, 45-74); male/female 7/20; never/current or former smoker 15/12; ECOG performance status 0/1 19/8; EGFR exon 19 deletion/exon 21 L858R 13/14; and c-stage IIIA/IIIB 14/13.

Participant flow

Between Aug 2012 and Nov 2017, 28 patients were enrolled and 27 were eligible and treated with the protocol therapy.

Adverse events

Pneumonitis was frequently observed, but all events were mild (Grade 1 59.2% and Grade 2 29.6%). Severe adverse events Grade 3-4 were increased ALT (59.3%), increased AST (37.0%), fatigue (3.7%), skin reaction (3.7%) and appetite loss (3.7%). Most of the severe adverse events was manageable liver dysfunction, and there was no treatment-related death.

Outcome measures

In this study, we set PFS rate at two-years as the primary endpoint. For sample size calculation, we assumed an improvement of PFS rate at 2 years from 20% to 40%. As a result, PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-), which did not meet the primary endpoint. ORR was 81.5% (95%CI: 63.3-91.3%). Median PFS was 18.6 months (95% CI: 12.0-24.5 months) and PFS rates at one-year was 66.7% (95% CI: 45.7-81.1%). Median OS was 61.1 months (95%CI: 38.1 months to not reached) and survival rate at one- and two-year was 100.0% and 96.3%, respectively.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2012

Year

07

Month

02

Day

Date of IRB

2012

Year

08

Month

27

Day

Anticipated trial start date

2013

Year

01

Month

24

Day

Last follow-up date

2020

Year

08

Month

20

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

07

Month

06

Day

Last modified on

2023

Year

05

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009835