Osimertinib combined bevacizumab in patients with non-small-cell lung cancer with malignant pleural and/or pericardial effusion -phase II trial-

JRCT ID: jRCTs071180004

Registered date:17/10/2018

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: advanced/recurrent non-small cell lung cancer (NSCLC)
• Date of first enrollment: 28/01/2019
• Target sample size: 30
• Study type: Interventional
• Intervention(s): 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).

Outcome(s)

• Primary Outcome: 1 year Progression free survival rate (1-year PFS rate)

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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 hemoptysis (expectoration of fresh blood more than 2.5mL/time to be caused by non-small-cell lung cancer) or the following bloody sputum.
bloody sputum which occurs continuously (more than one week)
bloody sputum which needs the continuous administration of oral hemostatics
(such as patients that oral hemostatics was necessary for again after having
been relieved using 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:
1) Mean resting mean corrected QT interval (QTC using Fredericia's formula)>470msec.
2) Any clinically important abnormalities in rhythm,conduction or morphology of resting ECG.(e.g.complete left bundle branch block,third degree heart block,second degree heart block)
3) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
Electrolyte imbalance(serum/plasma potassium level<3.6mmol/L,serum/plasma magnesium level<1.8mg/dL,serum/plasma calcium level<8.8mg/dL).
Patients with heart failure,congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or with any concomitant medication known to prolong the QT interval and induce Torsades de Points(TdP).
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.
(such as uncontrollable cardiac disease, severe cardiac arrhythmia to need medical treatment, sustained serious diarrhea)
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 (HIV) infection. In addition, it is not required that the test is carried out to confirm the presence or absence of these diseases.
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 or patients whose partner plans to become pregnant during a study period.
17. Any other patients who are regarded as unsuitable for this study by the investigators.

Related Information

• Primary Sponsor: Takayama Koichi
• Source(s) of Monetary Support: AstraZeneca K.K.
• Secondary ID(s): UMIN000028071