UMIN-CTR Clinical Trial

Public title

Osimertinib combined bevacizumab in untreated epidermal growth factor receptor mutaeted non-small-cell lung cancer patients with malignant pleural and/or pericardial effusion -phase II trial-

Acronym

SPIRAL II Study

Scientific Title

Osimertinib combined bevacizumab in untreated epidermal growth factor receptor mutaeted non-small-cell lung cancer patients with malignant pleural and/or pericardial effusion -phase II trial-

Scientific Title:Acronym

SPIRAL II Study

Region

Japan

Condition

advanced/recurrent non-small cell lung cancer (NSCLC)

Classification by specialty

Medicine in general	Pneumology	Hematology and clinical oncology
Chest surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

We evaluate the efficacy and safety on combination therapy of osimertinib and bevacizumab in patients with untreated epidermal growth factor receptor mutated non-small-cell lung cancer patients with malignant pleural and/or pericardial effusion..

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

1 year Progression free survival rate (1-year PFS rate)

Key secondary outcomes

Rresponse rate (RR)
Progression free survival (PFS)
Overall survival (OS)
Safety
Pleural or pericardial drainage free survival

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Osimertinib 80mg, po once daily and bevacizumab 15mg/kg, iv every 3 weeks are administered until PD as 21 days of 1 cycle (or the meeting of discontinuation criteria).

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

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Patients with untreated stage IV or post-operative recurrence who was histologically or cytologically confirned as non-small-cell lung cancer.(excluding squamous carcinoma) When chemotherapy is carried out in patients with post-operative recurrence, it is eligible if four weeks passed after the final treatment of prior chemotherapy. Radiation therapy in the case of radical radiation to chest:>=12 weeks after the day of final radiation. In the case of radiation to other than chest:>=2 weeks after the day of final radiation Operation/treatment(excluding chest drainage,pericardial drainage): >=4 weeks after the day of final operation/treatment Chest drainage,pericardial drainage:>=2 weeks after the day of treatment
2.Patients with malignant pleural and pericardial effusion.(in principle, cytodiagnosis is conducted. However, it is eligible when it can be clearly diagnosed as carcinomatous pleurisy and malignant pericardial effusion by image test and clinical surveillance even if a result of malignancy is not taken).
3.Patients with EGFR mutation positive.
4.Patients capable of treatment with oral medicine.
5.Patients have at least one measurable lesion accorring to RECIST v.1.1 criteria. 6.Performance Status(ECOG)0-2.
7.Patients capable of participating this study under at least 2 weeks admission to the hospital or corresponding management,in principle.
8.Patients are >=20 years of age (at informed consent).
9.Patients for whom bone marrow,hepatic, and renal functions have all been confirmed as normal within 14 days prior to enrollment according to the following clinical test standards(it is eligible on the same day 2 weeks before the enrolment days):
Neutrophil count >= 1.5x10^3/uL
Platelet count >= 100x10^3/uL
Hemoglobin >= 9.0 g/dl
AST, ALT <=100U/L
Total bilirubin <=1.5mg/dL
Creatinine <=2.0mg/dL
SpO2(Room air >=90%
Proteinuria <1+
10.Patients with life expectancy of at least 3 months.
11.Patients providing the written informed consent.

Key exclusion criteria

1.Patients whose chest drainage is no problem for pleural effusion,but who have pleurodesis.
2.Patients with pulmonary disorders such as idiopathic pulmonary fibrosis,interstitial pneumonia, pneumoconiosis,active radiation pneumonitis and drug-induced pneumonia. 3.Anamnesis and complication of hemoptysisor the following bloody sputum. bloody sputum which occurs continuously bloody sputum which needs the continuous administration of oral hemostatics bloody sputum necessary for homostatic injection. 4.Patients with cavity and tumor invasion to large vessels. 5.Infectious disorder need for intravenous injection of antibacterial drug and antimycotics. 6.Patients with corneal ulcer.7.Patients with any of the following risk of QTc prolongation:
Mean resting mean corrected QT interval >470msec. Any clinically important abnormalities in rhythm,conduction or morphology of resting ECG. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
8.Patients who are pregnant,nursing or possibly pregnant.
9.Patients with brain metastasis accompanying symptoms.
10.Active double cancer.
11.Patients with uncontrollable diabetes mellitus. 12.Patients who have complications to be clinical problem. 13.Patients judged as severe or uncontrollable systemic disease by investigators. For example,patients is judged by investigators that the participation in the study is undesirable or that the compliance of the protocol is difficult by uncontrollable hypertension and active hemorrhagic diathesis or hepatitis B,hepatitis C and active infections such as human immunodeficiency virus infection.
14.Patients with anamneses such as refractory nausea and vomiting,chronic digestive organ disease or pharmaceutical preparation aphagia,or gastroeneterectomy that may remarkably influence osimertinib absorption.
15.Patients whose wound healing cannot be confirmed.
16.Patients without intention to prevent pregnancy during a study period.

Target sample size

30

Name of lead principal investigator

1st name	Junji
Middle name
Last name	Uchino

Organization

Kyoto Prefectural University of Medicine

Division name

Department of Pulmonary Medicine

Zip code

602-8566

Address

465 Kajii-cho, Kamigyo-ku, Kyoto, Japan

TEL

075-251-5513

Email

uchino@koto.kpu-m.ac.jp

Name of contact person

1st name	Osamu
Middle name
Last name	Hiranuma

Organization

Otsu Municipal Hospital

Division name

Department of Respiratory Medicine

Zip code

520-0804

Address

2-9-9 Motomiya, Otsu, Shiga , Japan

TEL

077-522-4607

Homepage URL

Email

osamu319@true.ocn.ne.jp

Institute

Clinical Research Support Center Kyushu

Institute

Department

Personal name

Organization

AstraZeneca K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

JAPAN

Co-sponsor

Name of secondary funder(s)

Organization

Clinical Research Network Fukuoka Certified Review Board

Address

3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka

Tel

092-643-7171

Email

mail@crnfukuoka.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

京都府立医科大学付属病院（京都府）、地方独立行政法人総合病院国保旭中央病院（）、宇治徳洲会病院（京都府）、市立大津市民病院（滋賀県）、京都第一赤十字病院（京都府）、千葉西総合病院（千葉県）、社会医療法人鹿児島愛心会大隅鹿屋病院（鹿児島県）、医療法人徳洲会湘南藤沢徳洲会病院（神奈川県）、金沢医科大学病院（石川県）、福岡大学病院（福岡県）、京都山城総合医療センター（京都府）、国立病院機構東近江総合医療センター（滋賀県）、独立行政法人国立病院機構京都医療センター（京都府）、地方独立行政法人栃木県立がんセンター（栃木県）、和泉市立総合医療センター（大阪府）、藤田医科大学病院（愛知県）、医療法人徳洲会八尾徳洲会総合病院（大阪府）、JCHO京都鞍馬口医療センター（京都府）、国立病院機構金沢医療センター（石川県）、京都中部総合医療センター（京都府）、医療法人財団康生会武田病院（京都府）、京都府立医科大学附属北部医療センター（京都府）、JCHO神戸中央病院（兵庫県）、パナソニック健康保険組合松下記念病院（大阪府）、日本赤十字社京都第二赤十字病院（京都府）、帝京大学医学部附属病院（東京都）、市立福知山市民病院（京都府）、独立行政法人国立病院機構大牟田病院（福岡県）、京都大学医学部附属病院（京都府）、富山県立中央病院（富山県）、独立行政法人国立病院機構長崎医療センター（長崎県）、医療法人社団洛和会洛和会音羽病院（京都府）

Date of disclosure of the study information

2017

Year

07

Month

04

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

31

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

2017

Year

02

Month

28

Day

Date of IRB

2017

Year

05

Month

30

Day

Anticipated trial start date

2017

Year

07

Month

01

Day

Last follow-up date

2023

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

07

Month

04

Day

Last modified on

2023

Year

01

Month

10

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030717