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
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
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
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
