UMIN-CTR Clinical Trial

Public title

Randomized phase III study comparing erlotinib plus bevacizumab to erlotinib alone in patients with previously untreated non-small cell lung cancer harboring EGFR mutation (NEJ026)

Acronym

Randomized phase III study of erlotinib + bevacizumab vs erlotinib (NEJ026)

Scientific Title

Randomized phase III study comparing erlotinib plus bevacizumab to erlotinib alone in patients with previously untreated non-small cell lung cancer harboring EGFR mutation (NEJ026)

Scientific Title:Acronym

Randomized phase III study of erlotinib + bevacizumab vs erlotinib (NEJ026)

Region

Japan

Condition

Advanced non-squamous non-small cell lung cancer

Classification by specialty

Pneumology

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

to investigate the efficacy and the safety of erlotinib plus bevacizumab in comparison with erlotinib alone

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

Progression-free survival

Key secondary outcomes

Overall survival, response rate, disease control rate, duration of response, safety, QOL

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Erlotinib + Bevacizumab

Interventions/Control_2

Erlotinib

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)Histologically or cytologically documented non-squamous NSCLC
(2)EGFR (Exon 19 deletion or Exon 21 L858R) mutation status, detected with PCR, is active
(3)Stage IIIB or stage IV or recurrent NSCLC
(4)No prior systemic chemotherapy. Patients with history of treatment with anticancer drugs for pleurodesis are not eligible. If patients have received neoadjuvant / adjuvant chemotherapy, the patients who experience recurrence after 6 months are permitted
(5)Regarding the patients who have be treated with radiotherapy;
1)Not have received radiotherapy to lesions of lung
2)More than 2 weeks after receiving radiotherapy to lesions except lung
(6)Regarding the patients who have be treated with therapy as follows;
1)More than 4 weeks after the last operation
2)More than 2 weeks after the last pleurodesis except anticancer drugs
3)More than 2 weeks after the last biopsy with an incision
4)More than 2 weeks after the last treatment for injury
5)More than 2 weeks after the last systemic administration of steroid over 4 weeks
6)More than 4 weeks after the last administration of other investigational drugs
(7)Patients who have at least one or more measurable lesion by RESIST (Version1.1)
(8)Aged >=20, at the time of consent
(9)ECOG PS 0-2
(10)Have adequate organ function as follows;
1)neutrophil >=1,500/mm3
2)hemoglobin >=9.0g/dL
3)platelet >=100,000/mm3
4)bilirubin <=1.5mg/dL
5)AST/ALT <=2.5xULN
6)serum creatinine <=1.5mg/dL
7)PaO2(room air) >=70Torr or SpO2 >=94%
8)APTT <=ULN
9)PT-INR <=1.5
10)urine protein under 1+
(11)Written informed consent
(12)Estimated life expectancy at least 3 months

Key exclusion criteria

(1)Exon 20 T790M mutation status, detected with PCR, is active. Have received
(2)Have symptomatic brain metastasis
(3)Have a history of multiple malignancies within 5 years
(4)History of pulmonary hemorrhage or hemoptysis as defined below;
1)Hemosputum continuing for more than 1 week within 1 year before enrollment.
2)Have had or require continuous oral administration of hemostat
3)Have had or require injectable administration of hemostat
(5)Evidence of bleeding diathesis or hemoptysis
(6)Evidence of tumor invading a perihilar blood vessel or cavitation in intra-thoracic lesion on imaging
(7)Evidence of tumor invading segmental bronchus
(8)Uncontrolled pleural, ascites effusion or cardiac effusion
(9)Having a history or serious complications as bellows;
1)SVC syndrome complication
2)Spinal cord compression
3)Having a history of serious symptomatic cerebrovascular disease within 1 year before enrollment
4)Unrecovered fracture or severe injury
5)Have severe infection
6)Having a history or evidence of ILD complication on imaging or lung infection (except history of radiation pneumonitis in radiation area)
7)Have gastrointestinal dysfunction as follows;
<1>Impossible to take drugs orally
<2>Need intravenous feeding
<3>Have malabsorption by surgery
<4>Have active peptic ulcer
8)Have severe corneal disease complication
9)Have severe heart disease complication
10)Have diverticulitis
11)Have ever had a history of gastrointestinal perforation within 1 year prior to registration
12)Have severe neurological deficit or mental disorder
13)Have active hepatic disease
(10)Surgery planned in trial period
(11)Have a history of severe allergy of other monoclonal antibody drugs
(12)Have a history of EGFR TKI or anti-angiogenesis drug administration
(13)Pregnant or breast-feeding woman
(14)Patients who have no will to contraception
(15)Patients whose participation in the trial is judged to be inappropriate by the doctor

Target sample size

214

Name of lead principal investigator

1st name
Middle name
Last name	Makoto Maemondo

Organization

Iwate Medical University

Division name

Division of pulmonary medicine, allergy, and rheumatology

Zip code

Address

19-1 Uchimaru Morioka

TEL

019-651-5111

Email

maemondo-ma693@aioros.ocn.ne.jp

Name of contact person

1st name
Middle name
Last name	Tatsuro Fukuhara

Organization

Miyagi Cancer Center

Division name

Department of Respiratory Medicine

Zip code

Address

47-1 Nodayama, Medeshima-Shiode, Natori 981-1293

TEL

022-384-3151

Homepage URL

Email

mcc-konai@miyagi-pho.jp

Institute

North East Japan Study Group (NEJSG)

Institute

Department

Personal name

Organization

CHUGAI PHARMACUTICAL CO., LTD.

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

宮城県立がんセンター（宮城県）

Date of disclosure of the study information

2015

Year

04

Month

07

Day

URL releasing protocol

Publication of results

Partially published

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

No longer recruiting

Date of protocol fixation

2015

Year

03

Month

18

Day

Date of IRB

Anticipated trial start date

2015

Year

04

Month

20

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

04

Month

07

Day

Last modified on

2018

Year

08

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019773