UMIN-CTR Clinical Trial

Public title

A Phase II, Open Label, Randomized Study of Osimertinib (TAgrisso) alone Versus Osimertinib plus Carboplatin/Pemetrexed for Patients
With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose TUmours Harbour a T790M MutatIon Within the Epidermal Growth Factor Receptor Gene

Acronym

TAKUMI Trial
(LOGIK1604/NEJ032A)

Scientific Title

A Phase II, Open Label, Randomized Study of Osimertinib (TAgrisso) alone Versus Osimertinib plus Carboplatin/Pemetrexed for Patients
With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose TUmours Harbour a T790M MutatIon Within the Epidermal Growth Factor Receptor Gene

Scientific Title:Acronym

TAKUMI Trial
(LOGIK1604/NEJ032A)

Region

Japan

Condition

T790M-positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Classification by specialty

Chest surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To compare the efficacy and safety of osimertinib with or without carboplatin and pemetrexed in patients with non-squamous non-small-cell lung cancer refractory to EGFR-TKI treatment and confirmed as T790M-positive by tumor specimens after exacerbation, and to explore whether the combination of the third generation EGFR-TKI and chemotherapy is the appropriate therapeutic strategy to be verified in a phase III study.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

progression free survival

Key secondary outcomes

response rate,
overall survival,
incidence of adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Group A: Osimertinib monotherapy
Consecutively administer oral dose of osimertinib at 80 mg/day every day at almost the same time for 3 weeks as one course, and continue treatment unless any of the discontinuation criteria of protocol treatment is applicable.

Interventions/Control_2

Group B: Combination therapy with osimertinib
1.Combination therapy with osimertinib/carboplatin/pemetrexed
Three weeks of the following regimen will consist of one course and 4 courses will be repeated unless discontinuation criteria for protocol treatment is applicable. Qsimertinib at 80 mg/day will be orally administered every day at almost the same time.
Carboplatin (AUC=5) wiil be administered at day 1 every 3 weeks course.
Pemeterexed at 500 mg/m2 will be administered at day 1 every 3 weeks course.
2. Combination maintenance therapy with osimertinib/pemetrexed in the case of CR, PR SD
Three weeks of the following regimen will consist of one course and continue unless discontinuation criteria for protocol treatment is applicable.
Qsimertinib at 80 mg/day will be orally administered every day at almost the same time.
Pemeterexed at 500 mg/m2 will be administered at day 1 every 3 weeks course.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Clinical stage IIIB or IV or postoperative recurrent non-squamous non-small cell lung cancer harbouring susceptible EGFR mutations (G719X mutation, exon 19 deletion, L858R mutation, L861Q mutation) that cannot be treated with curative radiotherapy
2) Aggravation confirmed by imaging diagnosis after treatment with the first- and second-generation EGFR-TKI and T790M mutation confirmed in tumor tissue specimens or blood specimen after exacerbation
3) No history of treatment with cytotoxic drugs. However, the patients who received the final dose more than one year prior to enrollment are eligible in case of recurrence after pre-or postoperative adjuvant chemotherapy.
4) At least 8 days passed after the final dose of EGFR-TKI.
5) Aged 20 years or older at the time of informed consent
6) ECOG performance status (PS): 0 or 1
7) No palliative radiotherapy for metastatic lesion(s) (including gamma knife therapy for brain metastasis within 7 days) within 14 days before enrollment
8) No Grade 3 or higher superior vena cava syndrome, pericardial effusion, pleural effusion, or ascites
9) Irrespective of measurable lesion
10) All of the following criteria are met based on the laboratory data at the start of treatment (The data obtained within 14 days of enrollment: the same day of the week 2 weeks before enrollment is allowed):
1.WBC count:>=3000 /mm3
2.Neutrophil count:>=1500 /mm3
3.Hemoglobin:>= 9.0 g/dL (no blood transfusion within 14 days of screening)
4.Platelet count:>=10X10,000/mm3
5.AST:=< 100 IU/L
6.ALT:=< 100 IU/L
7.Total bilirubin:=< 1.5 mg/dL
8.SpO2:>=92 % (room air). Patients with SpO2 <92% are eligible if PaO2 is >=60 torr.
9.Creatinine:=<1.2 mg/dL
10. Creatinine clearance >=45 mL/min However, Ccr shall not exceed 120 (ml/min).
11)Have given written consent to participate in the study after receiving detailed explanation of the study

Key exclusion criteria

1) Active double cancer (simultaneous double cancer/multiple cancer, and metachronous double cancer/multiple cancer within 5 years of disease-free period. However, carcinoma in situ and a lesion equivalent to intramucosal carcinoma judged cured by local therapy are not included as active double cancer/multiple cancer).
2) Evidence of interstitial pneumonia or pulmonary fibrosis by chest CT scan /Radiation pneumonitis which required steroid treatment
3) Not able to swallow oral medications
4) Previous treatment history of immune checkpoint inhibitors
5) Infection requiring systemic treatment
6) Fever of >=38(axillary temperature) at the time of enrollment
7) Psychosis or psychotic symptoms that may interfere with the patient's participation in the study
8) Symptomatic brain metastasis (clinically stable brain metastasis is eligible)
9) Adverse event of >=Grade 2 considered attributable to EGFR-TKI of the prior therapy
10) Receiving continuous systemic (oral or intravenous) immunosuppressant therapy
11) Complication of diabetes mellitus treated with continued use of insulin or poorly controlled diabetes mellitus
12) Complication of unstable angina (new-onset angina or exacerbation of angina within the last 3 weeks) or history of myocardial infarction within 6 months.
13) HBs antigen-positive
14) Pregnant or possibly pregnant women, lactating women, or patients who wish to become pregnant
15) Patients who, in the opinion of the attending physician, are inappropriate for the study

Target sample size

90

Name of lead principal investigator

1st name
Middle name
Last name	(1) Isamu Okamoto,(2) Satoshi Oizumi

Organization

(1) Kyushu University,(2) National Hospital Organization Hokkaido Cancer Center

Division name

(1) Research Institute for Diseases of the Chest,(2) Department of Respiratory Medicine

Zip code

Address

(1) 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan,(2) 2-3-54, Kikusui4jo, Shiroishi-ku, Sapporo 003-0804, Japan

TEL

092-642-5378

Email

okamotoi@med.kyushu-u.ac.jp

Name of contact person

1st name
Middle name
Last name	(1) Kentaro Tanak,(2) Hajime Asahina

Organization

(1) Kyushu University,(2) Hokkaido University School of Medicine

Division name

(1) Research Institute for Diseases of the Chest,(2) First Department of Medicine

Zip code

Address

(1) 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan,(2) Nishi 7 Cho-me, Kita15jo, Kita-ku, Sappo

TEL

092-642-5378

Homepage URL

Email

tanaka-k@med.kyushu-u.ac.jp

Institute

Lung Oncology Group in Kyushu (LOGIK)/North East Japan Study Group(NEJSG)

Institute

Department

Personal name

Organization

AstraZenaca

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2016

Year

10

Month

17

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

08

Month

01

Day

Date of IRB

2016

Year

11

Month

09

Day

Anticipated trial start date

2016

Year

11

Month

09

Day

Last follow-up date

2020

Year

03

Month

05

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

10

Month

17

Day

Last modified on

2020

Year

04

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028092