UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000005556
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

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Basic information

Public 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)

Acronym

Phase I / II study for reduced dose of Erlotinib

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)

Scientific Title:Acronym

Phase I / II study for reduced dose of Erlotinib

Region

Japan


Condition

Condition

Lung adenocarcinoma having the sensitive mutation to EGFR-TKI

Classification by specialty

Pneumology Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

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

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I,II


Assessment

Primary outcomes

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.

Key secondary outcomes

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


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

Interventions/Control_1

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.

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)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

Key exclusion criteria

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

Target sample size

20


Research contact person

Name of lead principal investigator

1st name Yuichiro
Middle name
Last name Takeda

Organization

National Center for Global health and Medicine

Division name

Department of Respiratory Medicine

Zip code

162-865

Address

1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

TEL

03-3202-7181

Email

ytakeda@hosp.ncgm.go.jp


Public contact

Name of contact person

1st name Yuichiro
Middle name
Last name Takeda

Organization

National Center for Global health and Medicine

Division name

Department of Respiratory Medicine

Zip code

162-8655

Address

1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

TEL

03-3202-7181

Homepage URL


Email

ytakeda@hosp.ncgm.go.jp


Sponsor or person

Institute

Department of Respiratory Medicine
National Center for Global health and Medicine

Institute

Department

Personal name



Funding Source

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization



Other related organizations

Co-sponsor

Department of drug metabolism and disposition
Meiji pharmaceutical university

Name of secondary funder(s)

None


IRB Contact (For public release)

Organization

Center for Clinical sciences, National Center for Global health and Medicine

Address

1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

Tel

03-3202-7181

Email

rinrijim@hosp.ncgm.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

国立国際医療研究センター病院(東京都)


Other administrative information

Date of disclosure of the study information

2011 Year 05 Month 10 Day


Related information

URL releasing protocol

Clin Transl Sci. 2020 Apr 21. doi: 10.1111/cts.12796. Online ahead of print. PMID: 32315488

Publication of results

Published


Result

URL related to results and publications

http://www2.convention.co.jp/jca2017/

Number of participants that the trial has enrolled

38

Results

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.

Results date posted

2019 Year 03 Month 30 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2020 Year 04 Month 21 Day

Baseline Characteristics

EGFR-tyrosine kinase inhibitor naive patients with sensitizing mutations were eligible.

Participant flow

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).

Adverse events

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.

Outcome measures

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.

Plan to share IPD

We have no plan to share IPD.

IPD sharing Plan description

no plan


Progress

Recruitment status

Completed

Date of protocol fixation

2010 Year 06 Month 25 Day

Date of IRB

2010 Year 06 Month 25 Day

Anticipated trial start date

2010 Year 12 Month 01 Day

Last follow-up date

2017 Year 09 Month 01 Day

Date of closure to data entry

2017 Year 09 Month 07 Day

Date trial data considered complete

2017 Year 09 Month 11 Day

Date analysis concluded

2018 Year 06 Month 30 Day


Other

Other related information



Management information

Registered date

2011 Year 05 Month 05 Day

Last modified on

2020 Year 11 Month 28 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006584


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name