UMIN-CTR Clinical Trial

Public title

Randomized phase II study of osimertinib plus bevacizumab and osimertinib for chemotherapy-naive patients with nonsquamous non-small cell lung cancer harboring EGFR mutations (investigator-initiated multicenter clinical trial, WJOG9717L)

Acronym

Randomized phase II study for NSCLC(WJOG9717L)

Scientific Title

Randomized phase II study of osimertinib plus bevacizumab and osimertinib for chemotherapy-naive patients with nonsquamous non-small cell lung cancer harboring EGFR mutations (investigator-initiated multicenter clinical trial, WJOG9717L)

Scientific Title:Acronym

Randomized phase II study for NSCLC(WJOG9717L)

Region

Japan

Condition

Nonsquamous non-small cell lung cancer harboring EGFR mutations untreated by chemotherapy

Classification by specialty

Pneumology

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To compare the efficacy and safety of osimertinib plus bevacizumab with those of osimertinib alone in patients with advanced nonsquamous non-small cell lung cancer harboring EGFR mutations

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Progression-free survival (assessed by central image reviewers)

Key secondary outcomes

Progression-free survival (assessed by investigators), response rate, overall survival, incidence of adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Osimertinib+Bevacizumab

Interventions/Control_2

Osimertinib

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 confirmed nonsquamous NSCLC.
2) Confirmed EGFR mutations (exon 19 deletion, L858R) known to be associated with EGFR-TKI sensitivity with tumor tissue specimens or cytology specimens.
3) Absence of symptomatic brain metastases. Any brain metastasis with neurologic recovery by radiation therapy (corresponding to CTCAE v.4.0 grade 0 or 1) maintained for more than 2 weeks before enrollment (including the same day 2 weeks before) is acceptable.
4) Stage IIIB or IV not amenable to radical radiation therapy, or postoperative recurrence.
5) Age of 20 years or older at the time of informed consent.
6) ECOG performance status (PS) of 0 or 1
7) Presence of measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, excluding irradiated sites.
8) No prior chemotherapy for lung cancer (including EGFR-TKIs and immune checkpoint inhibitors).Any preoperative or postoperative chemotherapy given at least 6 months before enrollment in the present study is acceptable.
9) Absence of severe major organ involvement, with all of the following criteria met:
- Neutrophil count =>1500/mm3
- Hemoglobin =>9.0 g/dL
- Platelet count =>10.0x10,000/mm3
- PT-INR<=1.5
- AST <=100IU/L
- ALT <=100IU/L
- Total bilirubin <=1.5 mg/dL
- Creatinine <=1.5 mg/dL
- SPO2 =>90%(at room air)
- Urine protein <=1+
10) Written informed consent obtained from the patient after a sufficient explanation about the study given before enrollment in the study.

Key exclusion criteria

1)Active double cancers
2)Hemoptysis:
- Bloody sputum that occurs over 1 week
- Bloody sputum for which oral hemostatic drug was used continuously in the past 1 month or for which continuous use of oral hemostatic drug is required
- Bloody sputum for which injectable hemostatic drug was used in the past or for which use of injectable hemostatic drug is required
3) Highly likely to have the following bleeding complications:
- Bleeding tendency (coagulation disorder)
- Radiologically evident of tumor invasion of thoracic great vessels, cavitation of a lung lesion or thrombus
4) Antithrombotic drug that was used in the past 10 days or will be required during the study
5) Localized infection requiring surgical intervention or active systemic infection
6) Pregnant women, lactating women, women who may be pregnant, or women not intending to prevent pregnancy
7) Clinically significant psychiatric disorder that precludes the participation in the study
8) Continuous systemic administration of steroids at prednisolone-equivalent doses of >10 mg/day is required or current use of immunosuppressive drugs
9) History of serious hypersensitivity, or hypersensitivity to component of osimertinib or bevacizumab
10) Positive serum HBs antigen
11) Following concurrent or previous conditions:
- Symptomatic cerebrovascular accident
- Gastrointestinal perforation, fistula, or diverticulitis
- Difficult to take investigational drugs
- Symptomatic congestive heart failure or unstable angina, or previous myocardial infarction within 1 year before enrollment
- Mean QTc interval > 470ms, clinically severe arrhythmia, heart failure, hypokalemia , using medicine with risk of QTc prolongation or lethal arrhythmia
- Evident interstitial lung disease on CT, radiation pneumonitis
- Superior vena cava syndrome
- Spinal cord compression
- Untreated fracture or severe wound
- Uncontrolled peptic ulcer
- Hypertension uncontrolled by standard drug therapy (SBP >=150 mmHg or a DBP >=100 100 mmHg)

Target sample size

120

Name of lead principal investigator

1st name	Toshiaki
Middle name
Last name	Takahashi

Organization

Shizuoka Cancer Center

Division name

Thoracic Oncology

Zip code

411-8777

Address

1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture 411-8777 Japan

TEL

055-989-5222

Email

t.takahashi@scchr.jp

Name of contact person

1st name	Hirotsugu
Middle name
Last name	Kenmotsu

Organization

Shizuoka Cancer Center

Division name

Thoracic Oncology

Zip code

411-8777

Address

1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture 411-8777 Japan

TEL

055-989-5222

Homepage URL

Email

h.kenmotsu@scchr.jp

Institute

Coordinating committee for WJOG 9717L investigator-initiated clinical study

Institute

Department

Personal name

Organization

AstraZeneca K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

West Japan Oncology Group

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

Date of disclosure of the study information

2017

Year

12

Month

01

Day

URL releasing protocol

None

Publication of results

Published

URL related to results and publications

https://www.jto.org/article/S1556-0864(22)00265-9/fulltext

Number of participants that the trial has enrolled

122

Results

There was no statistically significant difference in PFS (primary endpoint) between osimertinib group and osimertinib+bevacizumab group.

Results date posted

2023

Year

07

Month

26

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2022

Year

05

Month

27

Day

Baseline Characteristics

Subjects were chemotherapy-naive patients with nonsquamous non-small cell lung cancer harboring sensitizing EGFR mutations. Age(median) and incidence of deletion in exon 19 were 66 and 59.0% in osimertinib group, and 67 and 57.4% in osimertinib+bevacizumab group. In patient characteristics, there was no difference between two groups.

Participant flow

Enrolled patients were 122 and randomly allocated to osimertinib group or osimertinib+bevacizumab group. Except one patient who was observed progression after randomization, 121 patients (60 patients in osimertinib group and 61 patients in osimertinib+ bevacizumab group) were received the study treatment allocated.

Adverse events

Major adverse events were as follows;
Osimertinib group: diarrhea, paronychia, rash, oral mucositis, leucopenia
Osimertinib+bevacizumab group: paronychia, diarrhea, oral mucositis, proteinuria, acneiform rash

Outcome measures

PFS(median): osimertinib group 20.2months, osimertinib+bevacizumab goup 22.1months (HR ratio 0.862 (60% confidence interval: 0.700-1.060, 95% confidence interval: 0.531-1.397), p=0.213)
ORR: osimertinib group 86.2%, osimertinib+bevacizumab group 82.0% (p=0.620)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

10

Month

06

Day

Date of IRB

2017

Year

11

Month

27

Day

Anticipated trial start date

2018

Year

01

Month

19

Day

Last follow-up date

2021

Year

07

Month

31

Day

Date of closure to data entry

2021

Year

11

Month

30

Day

Date trial data considered complete

2021

Year

12

Month

31

Day

Date analysis concluded

2022

Year

05

Month

26

Day

Other related information

Registered date

2017

Year

12

Month

01

Day

Last modified on

2023

Year

07

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034306