UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase II study of erlotinib plus bevacizumab and inserted cisplatin, pemetrexed plus bevacizumab as a 1st-line treatment for advanced non-squamous, non-small cell lung cancer harboring activating EGFR mutations
Title of the study (Brief title)	Phase II study of erlotinib plus bevacizumab and inserted cisplatin, pemetrexed plus bevacizumab as a 1st-line treatment for advanced non-small cell lung cancer harboring activating EGFR mutations
Region	Japan

Condition
Condition	advanced EGFR mutation-positive non-squamous non-small cell lung cancer
Classification by specialty	Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and the safety of the treatment of erlotinib plus bevacizumab and inserted cisplatin, pemetrexed plus bevacizumab as a 1st-line treatment for advanced non-squamous, non-small cell lung cancer harboring activating EGFR mutations
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	progression free survival
Key secondary outcomes	Overall survival, objective response rate, toxity, QOL,Exploratory purpose: using the next-generation sequencer, we examine the therapeutic effect over time and changes in circulating free DNA of EGFR gene mutations from plasma.

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	erlotinib plus bevacizumab and inserted cisplatin, pemetrexed plus bevacizumab as a 1st-line treatment
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	74 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Cytologically or histologically documented non-squamous non-small cell carcinoma of the lung 2) Harboring activating EGFR mutation (exon 19 deletion, and / or exon 21 L858R point mutation)or uncommon mutation (G719X or L861Q). 3) Have NSCLC with Stage IIIB, not candidate for curative radiotherapy, Stage IV or recurrence disease after surgery 4)No previous chemotherapy. If preoperative or postoperative adjuvant chemotherapy was done, it has passed more than six months from the last day of administration. 5)All of the following conditions is necessary if a patient has previously received radiation therapy. 1.Extra pulmonary fied 2.More than 12 weeks since prior radiotherapy to thoracic bones. 3.More than 2 weeks since prior radiotherapy to extra-thoracic sites. 6)If there is evaluable lesions or without measurable lesions. 7))>=20 and <=74 years of age. 8)ECOG performance status of 0 or 1. 9)Adequate organ function. 10)Written informed consent. 11)Expected survival of >= 3 months.
Key exclusion criteria	1)Harboring EGFR mutation of Exon20,T790M 2)Have symptomatic brain metastases or spinal metastases requiring surgical treatment or irradiation. 3)The presence of other concomitant malignancy less than 5 years disease-free interval 4)Have a pleural effusion, ascites or pericardial effusion requiring treatment 5)SVC syndrome 6)Symptomatic spinal cord compression 7)Currently have brain vascular disease with symptom, or have a history of it within one year before enrollment 8)Have sn unhealed fracture 9)Have a serious concomitant active infection 10)Have any evidence of interstitial lung on chest X-ray 11)Have a serious unstable angina, congestive heart failure, arrythmia requiring treatment and a history of myocardial infarction within 12 months prior to enrollment. 12)Clinically significant drug allergy 13)History of use of pemetrexed or EGFR-TKI as preoperative or postoperative adjuvant therapy 14)Pregnant or beeast-feeding woman or patient who doesn't agree to contraception 15) Mental disease or psychotic manifestation 16)Not suitable for participating in the study for any other reason 17)Currently have or have a history of hemoptysis 18) Patients with or with anticipation of invasive procedures as defined below: 1.Major surgery within four weeks of registration 2.two weeks after drainage tube removal 3.two weeks after pleurodesis 4.Minor surgical procedures or core biopsy within two weeks of registration etc. 19)Have a bleeding tendency 20)Have an intestinal diverticulitis 21)Have a history of gastrointestinal perforation less than one year prior to enrollment 22)Uncontrolable hypertension 23)Have a evidence of thrombosis 24)HBs antigen-positive cases Others
Target sample size	20

Research contact person
Name of lead principal investigator	Fumio Imamura
Organization	Osaka Medical Center for Cardiovascular diseases
Division name	Department of Thoracic Oncology
Address	1-3-3 Nakamichi Higashinari-ku, Osaka
TEL	0669711181
Email	imamura-fu@mc.pref.osaka.jp

Public contact
Name of contact person	Kazumi Nishino
Organization	Osaka Medical Center for Cardiovascular diseases
Division name	Department of Thoracic Oncology
Address	1-3-3 Nakamichi Higashinari-ku, Osaka
TEL	0669721181
Homepage URL
Email	nisino-ka@mc.pref.osaka.jp

Sponsor
Institute	Department of Thoracic Oncology Osaka Medical Center for Cardiovascular diseases
Institute
Department

Funding Source
Organization	no
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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	大阪府立成人病センター（大阪府）

Other administrative information
Date of disclosure of the study information	2014 Year 10 Month 18 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2014 Year 10 Month 10 Day
Anticipated trial start date	2014 Year 10 Month 20 Day
Last follow-up date	2016 Year 10 Month 19 Day
Date of closure to data entry	2018 Year 10 Month 19 Day
Date trial data considered complete	2018 Year 10 Month 19 Day
Date analysis concluded	2018 Year 10 Month 19 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2014 Year 10 Month 18 Day
Last modified on	2018 Year 10 Month 21 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017967