UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	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)
Title of the study (Brief title)	Randomized phase III study of erlotinib + bevacizumab vs erlotinib (NEJ026)
Region	Japan

Condition
Condition	Advanced non-squamous non-small cell lung cancer
Classification by specialty	Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
Primary outcomes	Progression-free survival
Key secondary outcomes	Overall survival, response rate, disease control rate, duration of response, safety, QOL

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Makoto Maemondo
Organization	Iwate Medical University
Division name	Division of pulmonary medicine, allergy, and rheumatology
Address	19-1 Uchimaru Morioka
TEL	019-651-5111
Email	maemondo-ma693@aioros.ocn.ne.jp

Public contact
Name of contact person	Tatsuro Fukuhara
Organization	Miyagi Cancer Center
Division name	Department of Respiratory Medicine
Address	47-1 Nodayama, Medeshima-Shiode, Natori 981-1293
TEL	022-384-3151
Homepage URL
Email	mcc-konai@miyagi-pho.jp

Sponsor
Institute	North East Japan Study Group (NEJSG)
Institute
Department

Funding Source
Organization	CHUGAI PHARMACUTICAL CO., LTD.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

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	宮城県立がんセンター（宮城県）

Other administrative information
Date of disclosure of the study information	2015 Year 04 Month 07 Day

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2015 Year 03 Month 18 Day
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

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 04 Month 07 Day
Last modified on	2018 Year 08 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019773