UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000014181 |
|---|---|
| Receipt number | R000016515 |
| Scientific Title | Prediction of adverse events in patients with EGFR-mutant non-small cell lung cancer using population pharmacokinetics of afatinib |
| Date of disclosure of the study information | 2014/06/06 |
| Last modified on | 2020/04/30 17:23:54 |
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Basic information
Public title
Prediction of adverse events in patients with EGFR-mutant non-small cell lung cancer using population pharmacokinetics of afatinib
Acronym
Population pharmacokinetics of afatinib
Scientific Title
Prediction of adverse events in patients with EGFR-mutant non-small cell lung cancer using population pharmacokinetics of afatinib
Scientific Title:Acronym
Population pharmacokinetics of afatinib
Region
| Japan |
Condition
Condition
EGFR-mutant non-small cell lung cancer
Classification by specialty
| Pneumology |
Classification by malignancy
Malignancy
Genomic information
YES
Objectives
Narrative objectives1
prediction of adverse event and efficacy using poplulation pharmacokinetics of afatinib
Basic objectives2
Pharmacokinetics
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Developmental phase
Not applicable
Assessment
Primary outcomes
correlation of adverse event and efficacy with plasma concentration of afatinib
Key secondary outcomes
correlation of response rate and progression-free survival with plasma concentration of afatinib,
correlation of adverse event and efficacy with T790M mutation
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine | Other |
Interventions/Control_1
Patients are treated with afatinib and serial blood samples are collected (drug concentrations and T790M mutation are investigated)
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
| Not applicable |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Eligibility criteria are as follows: (1) patients with EGFR-mutant non-small cell lung cancer adaptable to afatinib; (2)with written informed consent.; (3) without infection of HIV, HTLV, HBV, HCV, and TP.
Key exclusion criteria
Unsuitable cases are whom doctors jugde unable to be carried out this research safely.
Target sample size
80
Research contact person
Name of lead principal investigator
| 1st name | Shinji |
| Middle name | |
| Last name | Atagi |
Organization
National Hospital Organization Kinki-chuo Chest Medical Center
Division name
Department of Clinical Research Center
Zip code
591-8555
Address
1180 Nagasone, Kita-ku, Sakai, Japan
TEL
072-252-3021
s-atagi@kch.hosp.go.jp
Public contact
Name of contact person
| 1st name | Keiko |
| Middle name | |
| Last name | Nakao |
Organization
National Hospital Organization Kinki-chuo Chest Medical Center
Division name
Department of Internal Medicine
Zip code
591-8555
Address
1180 Nagasone, Kita-ku, Sakai, Japan
TEL
072-252-3021
Homepage URL
keinakao@kch.hosp.go.jp
Sponsor or person
Institute
National Hospital Organization Kinki-chuo Chest Medical Center
Institute
Department
Personal name
Funding Source
Organization
nothing
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
National Hospital Organization Kinki-chuo Chest Medical Center
Address
1180 Nagasone, Kita-ku, Sakai, Japan
Tel
072-252-3021
keinakao@kch.hosp.go.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
Other administrative information
Date of disclosure of the study information
| 2014 | Year | 06 | Month | 06 | Day |
Related information
URL releasing protocol
https://www.nature.com/articles/s41598-019-54804-9
Publication of results
Published
Result
URL related to results and publications
https://www.nature.com/articles/s41598-019-54804-9
Number of participants that the trial has enrolled
34
Results
Afatinib trough plasma concentrations on day 8 were higher in patients with adverse events of grade 3 or higher.
The population PK analysis showed that hepatic impairment affected afatinib PK parameters and contributed to the high inter-patient variability and high plasma concentrations of afatinib following multiple treatments.
Results date posted
| 2020 | Year | 04 | Month | 28 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
The population PK analysis was performed using plasma afatinib samples obtained from 34 patients with NSCLC, who started afatinib therapy at the National Hospital Organization Kinki-Chuo Chest Medical Center and the Osaka Habikino Medical Center between August 2014 and May 2016. All patients met the following criteria: cytologically or histologically confirmed as EGFR mutation-positive NSCLC, with no history of treatment with afatinib in previous chemotherapy. Patients who had undergone gefitinib or erlotinib treatments in the past were included.
Participant flow
Afatinib was orally administered at a dose of 40mg once daily until disease progression or intolerable toxicity. Physicians were able to increase the afatinib dose up to 50mg daily when they judged it was appropriate to increase the dose.
Adverse events
As expected, anorexia, diarrhea, skin complications, and stomatitis were the most frequently reported AEs. Grade 3 to 4 hematological toxicities (number; % of patients) included leukopenia (1; 2.9%) and neutropenia (1; 2.9%), whereas grade 3 to 4 nonhematological toxicities included anorexia (4; 11.8%), stomatitis (2; 5.9%), diarrhea (8; 23.5%), skin complications (3; 8.8%), pneumonitis (3; 8.8%), and infection (7; 20.6%).
Outcome measures
Patients who experienced grade 3 anorexia, grade 3 stomatitis, grade 3 or 4 diarrhea, and grade 3 skin complications showed higher trough plasma concentrations of afatinib on day 8 than patients who experienced under grade 2 AEs. In patients required dose reduction or interruption of afatinib, the trough plasma concentration of afatinib were significantly higher than that in those who did not require dose reduction or interruption.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2014 | Year | 06 | Month | 05 | Day |
Date of IRB
| 2014 | Year | 07 | Month | 25 | Day |
Anticipated trial start date
| 2014 | Year | 07 | Month | 25 | Day |
Last follow-up date
| 2016 | Year | 11 | Month | 30 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
correlation of adverse event and efficacy (response rate and progression-free survival) with plasma concentration of afatinib,
correlation of adverse event and efficacy with T790M mutation
Management information
Registered date
| 2014 | Year | 06 | Month | 05 | Day |
Last modified on
| 2020 | Year | 04 | Month | 30 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016515
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