Unique ID issued by UMIN | UMIN000005556 |
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Receipt number | R000006584 |
Scientific Title | Phase I / II study for appropriate dose of Erlotinib in patients with lung adenocarcinoma having the sensitive mutation to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI) |
Date of disclosure of the study information | 2011/05/10 |
Last modified on | 2020/11/28 15:37:58 |
Phase I / II study for appropriate dose of Erlotinib in patients with lung adenocarcinoma having the sensitive mutation to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI)
Phase I / II study for reduced dose of Erlotinib
Phase I / II study for appropriate dose of Erlotinib in patients with lung adenocarcinoma having the sensitive mutation to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI)
Phase I / II study for reduced dose of Erlotinib
Japan |
Lung adenocarcinoma having the sensitive mutation to EGFR-TKI
Pneumology | Hematology and clinical oncology |
Malignancy
NO
To find the minimum effective dose of Erlotinib which achieve the disease control (DC) without growth in patients with lung adenocarcinoma having sensitive EGFR-TKI mutation
Safety,Efficacy
Exploratory
Pragmatic
Phase I,II
1) Phase I; To find the minimum effective dose(MED) of Erlotinib
2) Phase II; The rates of DC(Disease Control) without growth on the MED after 6 to 8 weeks later.
1)Phase I; Adverse effects on the MED
2)Phase II; QOL questionnaires, pharmacokinetics, progression free survival (PFS), and the rates of adverse effects and response on the MED
Interventional
Single arm
Non-randomized
Open -no one is blinded
Uncontrolled
1
Treatment
Medicine |
Phase I; Dose reduction is guided following a Continual Reassessment Method (CRM) based on effect and toxicity. Starting dose of erlotinib is decided by the dose reduction plan. Evaluation of efficacy and toxicity is determined between 6 and 8 weeks. After evaluation of starting dose, efficacy and toxicity data are used to estimate the parameters that define the dose-efficacy / toxicity curve to determine the next dose. Repeating above process, minimum effective dose of erlotinib is determined. In day 1, Erlotinib is orally administered. Pharamacokinetics of erlotinib is performed from day 1 to 2. From day 3, erlotinib is orally administered once every day.
Phase II; Minimum effective dose determined by phase I study is given at day 1. Patients are not given erlotinib but carefully observed in day 2. Pharamacokinetics of erlotinib is performed from day 1 to 2. Erlotinib is orally administered once every day from day 3. Evaluation of efficacy and toxicity is determined between 6 and 8 weeks. Safety is assessed around every 4 weeks. Efficacy is evaluated around every 2 to 6 months. Treatment by minimum effective dose will be continued until severe toxicities or disease progression.
20 | years-old | <= |
Not applicable |
Male and Female
1)Histologically or cytologically proven lung adenocarcinoma
2)Stage IIIB/IV(UICC ver.7) or recurrence after surgical treatment
3)Tumor has sensitive mutation for EGFR-TKI
4)Naive treatment of EGFR-TKI
5)Tumor has the evaluable lesion
6)Eastern Cooperative Oncology Group performance status of 0-2
7)Age; > or = 20 years and < 80 years
8)Adequate organ function, Adequate organ function
Leukocyte count; > or = 3,000/mm3
Hemoglobin concentration; > or = 10.0g/dl
Platelet count; > or = 100,000/mm3
Total bilirubin level; < or = 2.0 mg/dl
Aspartate aminotransferse and alanine aminotransferase levels; < or = 100 IU/L
Creatinine clearance; > or = 30mL/min
Or serum creatinine; < or = 1.5 mg/dl
PaO2; > or = 70 torr at room air
9)Neither overt interstitial pneumonia nor overt lung fibrosis
10)Written informed consent
1)Uncontrollable comorbid disease.
2)Symptomatic brain metastases
3)Active concomitant malignancy
4)Active infectious disease
5)Pregnant status or lactation
6)Acute or chronic diarrhea
7)Clinically active interstitial pneumonia
8)Acute myocardial ischemia within 3 months or unstable angina pectoris
9)Other ineligible status judged by medical oncologist
20
1st name | Yuichiro |
Middle name | |
Last name | Takeda |
National Center for Global health and Medicine
Department of Respiratory Medicine
162-865
1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
03-3202-7181
ytakeda@hosp.ncgm.go.jp
1st name | Yuichiro |
Middle name | |
Last name | Takeda |
National Center for Global health and Medicine
Department of Respiratory Medicine
162-8655
1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
03-3202-7181
ytakeda@hosp.ncgm.go.jp
Department of Respiratory Medicine
National Center for Global health and Medicine
None
Self funding
Department of drug metabolism and disposition
Meiji pharmaceutical university
None
Center for Clinical sciences, National Center for Global health and Medicine
1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
03-3202-7181
rinrijim@hosp.ncgm.go.jp
NO
国立国際医療研究センター病院(東京都)
2011 | Year | 05 | Month | 10 | Day |
Clin Transl Sci. 2020 Apr 21. doi: 10.1111/cts.12796. Online ahead of print. PMID: 32315488
Published
http://www2.convention.co.jp/jca2017/
38
Safety and efficacy committee were held in October 25th 2013. According to their opinion, we collected additional information. They decided the recommended dose of expanded phase II portion in Dec 27th 2013 by these data. The phase II portion began in Dec 25th 2013. As to Dec 31th 2016,20 patients have registered in phase II portion. Allocation completed already.
2019 | Year | 03 | Month | 30 | Day |
2020 | Year | 04 | Month | 21 | Day |
EGFR-tyrosine kinase inhibitor naive patients with sensitizing mutations were eligible.
We decided not only clinical optimal dose by Phase I/II study based on continual reassessment method (CRM) both disease control and dose-limiting toxicity defined as any toxicities > or = Grade 2 (G2) within 8 weeks, but also pharmacological optimal dose by pharmacokinetics (PK).
In the safety analysis, we included all patients who had received at least one dose of study drug. The most common AEs with erlotinib were dermatologic toxicity and diarrhea. With the exception of liver toxicity, the frequency and grade of AEs decreased with decreasing daily dose of erlotinib (Supplementary Table S1). Only one patient developed grade 1 pneumonitis and recovered after cessation of treatment. Each patient, even among those receiving the same daily dose, exhibited a wide range of toxicities. TOX was defined as the percent duration of any type of AE > or = G2 during the progression free survival period. TOX10, TOX20, and TOX30 were defined as > or = 10, 20, or 30% duration of any type of AE > or = G2 during the PFS period, respectively. TOX10 to TOX30 tended to decrease with decreasing daily dose. In phase II, the percentage of TOX10 to TOX30 decreased in phase II.
Clinical and pharmacologic optimal doses were 25 by CRM and 50-60 mg/day by PK, respectively. At reduced starting dose, patients require personalized adjustment of 0.15-0.31 microgram /mL based on trough concentration as determined by population PK monitoring.
We have no plan to share IPD.
no plan
Completed
2010 | Year | 06 | Month | 25 | Day |
2010 | Year | 06 | Month | 25 | Day |
2010 | Year | 12 | Month | 01 | Day |
2017 | Year | 09 | Month | 01 | Day |
2017 | Year | 09 | Month | 07 | Day |
2017 | Year | 09 | Month | 11 | Day |
2018 | Year | 06 | Month | 30 | Day |
2011 | Year | 05 | Month | 05 | Day |
2020 | Year | 11 | Month | 28 | Day |
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006584
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