UMIN-CTR Clinical Trial

Public title

A prospective, phase II trial of low-dose afatinib monotherapy for patients with EGFR, mutation-positive, non-small cell lung cancer(TORG1632).

Acronym

Low-dose afatinib phase II study patients with EGFR Mutation-positive NSCLC(TORG1632)

Scientific Title

A prospective, phase II trial of low-dose afatinib monotherapy for patients with EGFR, mutation-positive, non-small cell lung cancer(TORG1632).

Scientific Title:Acronym

Low-dose afatinib phase II study patients with EGFR Mutation-positive NSCLC(TORG1632)

Region

Japan

Condition

Non-small Cell Lung Cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate the efficacy and safety of low dose afatinib in patients with EGFR-mutant NSCLC.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Progression Free Survival

Key secondary outcomes

-Response rate
-Disease control rate
-One-year PFS rate
-Overall survival
-Time to treatment failure
-AE rate

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

Afatinib is prescribed at 20mg/day daily
If SD or =<AE Grade1, this dose can be increased after 8 weeks of treatment, and repeated up to 50mg

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

Not applicable

Gender

Male and Female

Key inclusion criteria

1)Histologicaly or cytologically confirmed Stage IV or recurrent non-small cell lung cancer
2)Harboring sensitive EGFR mutation(Exon 19 deletion,L858R)
3)No prior chemotherapy and EGFR-TKI
4)Measurable disease for RECIST ver.1.1
5)Aged equal and more than 20 years old.
6)ECOG PS 0-2
7)Life expectancy: more than 3 months
8)Informed consent
9)Adequate organ functions judged by laboratory tests
i.ANC >= 1,500 mm3
ii.Hb >= 9.0g/dl
iii.PLT >= 75,000 mm3
iv.T-bil < 1.5 mg/dl
v.AST < 100 IU/L
vi.ALT< 100 IU/L
vii.SpO2 >= 93 %

Key exclusion criteria

1)Prior chemotherapy, GFR-TKI, biological drug and any investigational drug within 4 weeks.
2)Prior hormone therapy within 2 weeks.
3)Patients received radiotherapy for primary region and/or evaluable region.
4)Patients with major operation history within 4 weeks or planned during treatment period/
5) Patients with apparent interstitial pneumonia or pulmonary fibrosis on chest computed tomography
6)Symptomatic brain metastases
7)Uncontrolled complications
8)Treatment needed infection
9)Patients with hepatic cirrhosis or HIV
10)Patients with active double cancer less than 5 years
11)Patients with significant malabsorption syndrome
12)Pregnancy, breastfeeding or suspected of being pregnant
13)Patients who are considered to have difficulty in enrollment of this trial based on clinically important psychiatric reasons
14)Patients with a history of allergy for a component of afatinib

Target sample size

52

Name of lead principal investigator

1st name	Kaoru
Middle name
Last name	Kubota

Organization

Graduate School of Medicine, Nippon Medical School, Nihon Medical School Hospital

Division name

Department of Pulmonary Medicine and Oncology

Zip code

113-8602

Address

Sendagi 1-1-5, Bunkyo, Tokyo

TEL

03-3822-2131

Email

kkubota@nms.ac.jp

Name of contact person

1st name	Rintaro
Middle name
Last name	Noro

Organization

Graduate School of Medicine, Nippon Medical School, Nihon Medical School Hospital

Division name

Department of Pulmonary Medicine and Oncology

Zip code

113-8602

Address

Sendagi 1-1-5, Bunkyo, Tokyo

TEL

03-3822-2131

Homepage URL

Email

r-noro@nms.ac.jp

Institute

Thoracic Oncology Research Group

Institute

Department

Personal name

Organization

Thoracic Oncology Research Group

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Institutional Review Board of Nippon Medical School Foundation

Address

Sendagi 1-1-5, Bunkyo, Tokyo

Tel

03-5802-866

Email

officetokutei@nms.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

2017

Year

05

Month

15

Day

URL releasing protocol

-

Publication of results

Published

URL related to results and publications

https://doi.org/10.1016/j.lungcan.2021.08.007

Number of participants that the trial has enrolled

53

Results

The median PFS, and overall survival were 12.6 months (90% confidence interval [CI]: 9.7-4.3 months), and not reached, respectively. The primary endpoint was met. The objective response rate and disease control rate were 66.0% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9), respectively. Grade3 and above adverse events occurred in 12 patients (22.6%), including diarrhea in four patients (7.5%). The rate of adverse events was lower than that observed in previous phase III studies of 40 mg afatinib.

Results date posted

2022

Year

08

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The median age of 53 enrolled patients was 70 years old (range, 37-85), and 17, 29 and 7 patients had PS 0, PS 1 and PS 2, respectively. Twenty eight patients (52.8%) were women. The patients with stage IV and postoperative recurrence, are 47 and 6, respectively. EG FR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%).

Participant flow

The enrollment of this trial has been successfully completed within a scheduledperiod of time. Forty-four of 53 patients had completed the treatment according to the discontinuation criteria. Most of the reasons for discontinuation were progressive disease (33 patients). Only 7 patients received afatinib with escalated dose. The dose was reduced to 20 mg every other day in 5 patients. The median time on treatment was 291 days.

Adverse events

AEs were evaluated in all enrolled patients. Only five patients (9.4%) switched to treatment with 20 mg afatinib on alternate days due to AEs. Non-hematologic AEs in patients who experienced one event of grade3 and above occurred in 12 patients (22.6%). Grade3 and above AEs were diarrhea and paronychia reported by four patients (7.5%) and one patient (1.9%), respectively. Of note, grade3 and above rash/acne was not reported in this study. Two patients (3.8%) developed drug-related interstitial lung disease or an interstitial lung diseaselike event, leading to discontinuation of treatment. There was no treatment-related death noted in this study.

Outcome measures

The primary endpoint (PE) was progression-free survival (PFS). The threshold median PFS was 9.2 months and we investigated whether the median PFS was longer than the threshold median PFS or not. Treatment-naive patients with advanced NSCLC positive for common EGFR mutations received afatinib in a dose of 20 mg/day. If the tumor had grown within SD, the dose could be increased up to maximum 50 mg. The PFS by the PD confirmed day after the maximum dose increase and the PFS when the dose had to be increased from 20 mg were calculated according to our protocol. The median PFS was 12.6 months (90% Cl: 9.7- 14.3) and the PEwas met. The objective response and the disease control rates were 67.9% (36/53) and 92.5% (49/53).
Four of 13 patients (30.8%) had T790M resistant mutation by plasma circulating DNA mutational analyses. The median afatinib plasma concentrations at 9 days after the start of administration was 9.4 ng/ml.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

02

Month

17

Day

Date of IRB

2017

Year

03

Month

23

Day

Anticipated trial start date

2017

Year

05

Month

15

Day

Last follow-up date

2020

Year

02

Month

29

Day

Date of closure to data entry

2020

Year

05

Month

31

Day

Date trial data considered complete

2020

Year

08

Month

31

Day

Date analysis concluded

2020

Year

11

Month

30

Day

Other related information

Registered date

2017

Year

05

Month

14

Day

Last modified on

2022

Year

09

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031085