UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000024198
Receipt number R000027500
Scientific Title Frequency of T790M Mutation on Circulating Tumor DNA in EGFR-mutated NSCLC Patients With acquired resistance to irreversible EGFR-TKI :a prospective observational study
Date of disclosure of the study information 2016/10/01
Last modified on 2023/03/01 15:15:40

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Basic information

Public title

Frequency of T790M Mutation on Circulating Tumor DNA in EGFR-mutated NSCLC Patients With acquired resistance to irreversible EGFR-TKI :a prospective observational study

Acronym

Frequency of T790M Mutation on ctDNA in patients with acquired resistance to irreversible EGFR-TKI

Scientific Title

Frequency of T790M Mutation on Circulating Tumor DNA in EGFR-mutated NSCLC Patients With acquired resistance to irreversible EGFR-TKI :a prospective observational study

Scientific Title:Acronym

Frequency of T790M Mutation on ctDNA in patients with acquired resistance to irreversible EGFR-TKI

Region

Japan


Condition

Condition

EGFR-mutated Non Small Cell Lung Cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

YES


Objectives

Narrative objectives1

Analysis of the Frequency of T790M Mutation on Circulating Tumor DNA in EGFR-mutated NSCLC Patients With acquired resistance to irreversible EGFR-TKI

Basic objectives2

Others

Basic objectives -Others

Evaluation of the relationship between effect of irreversible EGFR-TKI and T790M mutation status

Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

Frequency of T790M Mutation on ctDNA in patients with acquired resistance to irreversible EGFR-TKI

Key secondary outcomes

Evaluation of the relationship between effect of irreversible EGFR-TKI and T790M mutation status


Base

Study type

Observational


Study design

Basic design


Randomization


Randomization unit


Blinding


Control


Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

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



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

1 Patients whose plasma samples can be submitted
2 Pathologically confirmed Nonsquamous Non Small Cell Lung Cancer
3 Clinical stage 3B, 4, or postoperative recurrence
4 With activating EGFR mutation, Deletion in exon 19 or L858R in exon 21
5 Patients with no treatment of EGFR-TKI and planned to EGFR-TKI treatment
6 Regarding the patients who have be treated with radiotherapy
-Not have received radiotherapy to lesions of lung
-More than 12 weeks after receiving radiotherapy to Sternal lesions
-More than 2 weeks after receiving radiotherapy to lesions except lung
7 Regarding the patients who have been treated with therapy as follows
-Surgical procedure, including exploratory thoracotomy, more than 4 weeks
-Pleural drainage, more than 2 weeks
-Pleurodesis except anticancer drugs, more than 2 weeks
-AnticancerDrugs, more than 3 weeks
8 Performance Status (ECOG) 0-2
9 Expecte survival time is more than 3 months
10 With adequate organ function
11 Provided written informed consent
12 Ages 20 years and over

Key exclusion criteria

1 Patients with pre-treatment of EGFR-TKI
2 Exhibiting significant interstitial pneumonitis, or pulmonary fibrosis in the chest X-ray
3 Synchronous double or multiple cancer or metachronous double or multiple cancer
4 Uncontrolled pleural, ascites effusion or cardiac effusion
5 Patients with active co-morbidities including severe conditions.
-Uncontrollable angina pectoris, myocardial infarction within 3 months, heart failure
-Uncontrolled diabetes mellitus, hypertension
-Severe infection
-Patients whose participation in the trial is judged to be inappropriate by the attending doctor
-Any other patients who are regarded as unsuitable for this trial by the attending doctor

Target sample size

30


Research contact person

Name of lead principal investigator

1st name Nobuaki
Middle name
Last name Kobayashi

Organization

Graduate school of medicine, Yokohama city university

Division name

department of pulmonology

Zip code

2360004

Address

3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, JAPAN

TEL

045-787-2508

Email

nkobayas@yokohama-cu.ac.jp


Public contact

Name of contact person

1st name Hideyuki
Middle name
Last name Nagakura

Organization

Graduate school of medicine, Yokohama city university

Division name

department of pulmonology

Zip code

2360004

Address

3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, JAPAN

TEL

045-787-2508

Homepage URL


Email

hdng8315@yokohama-cu.ac.jp


Sponsor or person

Institute

Yokohama city university

Institute

Department

Personal name



Funding Source

Organization

Nippon Boehringer Ingelheim Co.,Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Yokohama City University Ethics Committee

Address

3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004

Tel

045-370-7627

Email

rinri@yokohama-cu.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

横浜市立大学附属病院


Other administrative information

Date of disclosure of the study information

2016 Year 10 Month 01 Day


Related information

URL releasing protocol

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10135-z

Publication of results

Published


Result

URL related to results and publications

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10135-z

Number of participants that the trial has enrolled

30

Results

Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of 18 patients (22.2%) who reached progressive disease were positive EGFR T790M mutations. Only two patients were positive for major EGFR mutations at intermediate levels.

Results date posted

2023 Year 03 Month 01 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

This prospective observational study enrolled 30 patients between August 2016 and April 2021. Baseline characteristics and safety data were analyzed in an intention-to-treat (ITT) population. The median age of the patients was 69.0 years (range 54-82). Pathologically, 28 (93.3%) patients had adenocarcinoma, and two (6.6%) had adenosquamous carcinoma. Regarding performance status, 22 (73.3%), six (20.0%), and two (6.6%) patients had Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2, respectively. Regarding clinical stages, two patients were stage IIIB, 21 patients were stage IV, and 7 patients had postoperative recurrence. Regarding EGFR gene mutations, 25 (83.3%) patients had a 19del mutation, and five (16.6%) had an L858R mutation. At the time of enrollment, EGFR mutations in the blood were detected in 19 patients (63.3%).

Participant flow

30 patients were enrolled, all with tumor and liquid biopsies at enrollment. A total of five patients were excluded: three had adverse events, one was unwilling to participate, and one died shortly after starting. 18 patients underwent an interim liquid biopsy. After the interim liquid biopsy, 7 patients were also excluded: three did not reach PD, three had adverse events, and one was unwilling to participate. Finally, 18 patients reached progressive disease, of whom 18 had liquid biopsy and 10 had tumor re-biopsy.

Adverse events

The adverse events associated with afatinib observed in this study were similar to those reported previously. Grade 3 adverse events occurred in 10 patients (33.3%). No grade 4 or treatment-related deaths were observed. Afatinib was terminated in six patients (20%) due to adverse events.

Outcome measures

Primary endpoint: Frequency of T790M Mutation in ctDNA
Secondary endpoint: Concordance rate for activating mutations of liquid biopsy in comparison with tumor biopsy, Prediction of the treatment effectiveness with EGFR-TKI by liquid biopsy during treatment

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Main results already published

Date of protocol fixation

2016 Year 08 Month 24 Day

Date of IRB

2016 Year 08 Month 24 Day

Anticipated trial start date

2016 Year 10 Month 01 Day

Last follow-up date

2021 Year 04 Month 30 Day

Date of closure to data entry

2021 Year 06 Month 30 Day

Date trial data considered complete

2021 Year 10 Month 31 Day

Date analysis concluded

2022 Year 03 Month 31 Day


Other

Other related information

Study design:
Prospective cohort study
Object recruitment:
From October 2016 to June 2018, all patients who visit our facility and meet the inclusion criteria from October 2015 to September 2017.
Parameter measurement:
#1 T790M Mutation on ctDNA in patients with acquired resistance to irreversible EGFR-TKI before treatment, under treatment and disease progression
#2 Evaluation of the relationship between effect of irreversible EGFR-TKI and T790M mutation status


Management information

Registered date

2016 Year 09 Month 28 Day

Last modified on

2023 Year 03 Month 01 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027500


Research Plan
Registered date File name

Research case data specifications
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Research case data
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