UMIN-CTR Clinical Trial

Public title

Docetaxel plus Ramucirumab with pegylated granulocyte-colony stimulating factor support for elderly patients with advanced non-small cell lung cancer: A multicenter prospective single arm phase II study: DRAGON study(WJOG9416L)

Acronym

DOC+RAM+PEG-G-CSF in elderly NSCLC

Scientific Title

Docetaxel plus Ramucirumab with pegylated granulocyte-colony stimulating factor support for elderly patients with advanced non-small cell lung cancer: A multicenter prospective single arm phase II study: DRAGON study(WJOG9416L)

Scientific Title:Acronym

DOC+RAM+PEG-G-CSF in elderly NSCLC

Region

Japan

Condition

Non-small cell lung cancer

Classification by specialty

Pneumology	Hematology and clinical oncology	Geriatrics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the efficacy and safety of DOC+RAM with PEG-G-CSF support in chemo-naive elderly patients (aged 75) with NSCLC

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Response rate

Key secondary outcomes

Progression-free survival, overall survival, and safety

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

Central registration

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

DOC(60 mg/m2, day 1)+ RAM(10 mg/kg, day 1)&PEG-G-CSF(3.6 mg, day 2-4) every 3 weeks until progression or both DOC and RAM termination

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

75

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Aged <= 75
2.Written informed consent
3.Histologically or cytologically confirmed NSCLC
4.Stage IIIb without indication of definitive chemoradiotherapy, stage IV, or recurrence after surgery
5.Presence of measurable lesions
6.No symptomatic brain metastases and/or spiral metastases with requirement of surgery
7.No symptomatic superior vena cava syndrome
8.No uncontrolled cardiac, pleural, or abdominal effusion
9.No radiographic findings of ramucirumab restriction
I. No cancer invasion to major vessels and/or major vessel stenosis
II. No cavitation regardless of histology
III. No tumor exposure to main bronchus
10.ECOG PS 0/1
11.Normal labo data
WBC >= 3,000/mm3
Neut >= 1,500/mm3
Hb >= 9.0 g/dL
Plt >= 10 x 10^4 / mm3
T-bil <= 1.5 mg/dL
AST/ALT <= 100 IU/L (<= 200 IU/L by liver metastases)
CRE <= 1.5 mg/dL
PT-INR <= 1.5
SpO2 <= 92%
Protein uria <= 1+
12.No active hepatitis B infection
13.No history of receiving cytotoxic chemotherapies and ramucirumab
14.Recurrent cases after surgery, 1 prior adjuvant chemotherapy is permitted
15.No history of recent surgery
16.Interval >= 7 days after palliative radiation therapies
17.No prior chest radiotherapy for primary disease
18.No history of chest radiotherapy and chemotherapy against cancers other than primary disease

Key exclusion criteria

1) Active multiple cancer
2) Active infection
3) Interstitial pneumonia/pulmonary fibrosis
4) Uncontrolled diabetes
5) Uncontrolled hypertension
6) Clinically significant heart failure or uncontrolled arythmia
7) Ileus, inflammatory bowel disease, or chronic diarrhea
8) Uncontrolled thromboembolism
9) HIV associated disease
10) Severe psychological disease
11) Severe liver dysfunction such as cirrhosis
12) Prescription of steroids and/or immunosuppressant
13) Anticoaglation with warfarin or heparin
14) Prescription of long-term NSAIDS or antiplatelets
15) Fever >= 38.0 degrees C
16) Recent history of hemoptysis
17) Recent history of cardio-brain vascular disease
18) Incurable wound, ulcer, or bone fracture
19) Recent history of bleeding, vasculitis, or gastrointestinal hemorrhage
20) Recent history of gastrointestinal perforation/fistula
21) History of hypersensitivity by agents containing polysorbate 80
22) Plan of major surgery during the trial

Target sample size

65

Name of lead principal investigator

1st name	Akito
Middle name
Last name	Hata

Organization

Kobe Minimally Invasive Cancer Center

Division name

Department of Thoracic Oncology

Zip code

6500046

Address

8-5-1, Minatojima-minamimachi, Chuo-ku,Kobe

TEL

078-304-0041

Email

akitohata@hotmail.com

Name of contact person

1st name	Shinichiro
Middle name
Last name	Nakamura

Organization

West Japan Oncology Group

Division name

WJOG datacenter

Zip code

556-0016

Address

Namba Plaza Bldg. 304-1-5-7, Motomachi Naniwa-ku, Osaka 556-0016 JAPAN

TEL

06-6633-7400

Homepage URL

Email

datacenter@wjog.jp

Institute

West Japan Oncology Group

Institute

Department

Personal name

Organization

Eli Lilly Japan

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Wakayama Medical University Institutional Review Board

Address

811-1, Kimiidera, Wakayama, Wakayama-prefecture

Tel

073-441-0896

Email

wa-rinri@wakayama-med.ac.jp

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

27

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs051180232

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/37822699/

Number of participants that the trial has enrolled

54

Results

Response rate as primary endpoint: 0 complete response/ 21 partial response was confirmed in 54 cases, resulting in RR of 38.9% (90% confidence interval [CI], 27.7-51.0% and 95% CI, 25.9-53.1%). Since target-enrollment was not completed, statistical interpretation cannot be concluded. This result was over expected RR, and its effectiveness might be promising.

Results date posted

2024

Year

03

Month

06

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Median age : 78(range, 75-86) Male/Female : 43/11 Never smoker/Former smoker/Current smoker : 12/31/11 Histology Adenocarcinoma/Squamous/Others : 40/8/6 PS 0/1 : 20/34 EGFR mutation Positive/Negative/Unknown : 6/45/3 Stage III/Recurrence/IV : 3/15/36 Prior chemotherapy Chemo-naive/ICI/EGFR-TKI/Adjuvant chemo : 43/5/4/3 Prior surgery Received/None : 16/38 Prior radiation Received/None : 10/44

Participant flow

Initial sample size was set at 65 cases for 2 years. However, enrollment was not completed, and the period was extended with additional 1 year. During study period, standard of care was changed by positive study of carboplatin plus pemetrexed vs. docetaxel monotherapy and approval of first-line immunotherapies. Final enrollment was 54 cases before full accrual.

Adverse events

Serious adverse events (AEs) were reported in 12 cases (1 death and 11 hospitalizations or extended admission), of which 9 AEs were judged to be causally related to the treatment and 3 judged not to be causally related. The outcome was recovery or mild recovery in 10 cases; no recovery in 1 cases (causally non-related AE); and treatment-related death (TRD) in 1 case (drug induced interstitial lung disease [ILD] as a known AE). None of new unknown AEs were reported. One (1.9%) febrile neutropenia (FN) and 3 (5.6%) neutropenia grade >=3 were observed. ILD was confirmed in 5 (9.3%) cases,and one (1.9%) resulted in TRD. None of grade 4 non-hematological AEs were found. Pulmonary hemorrhage was observed in 5 (9.3%) cases, but all were grade 1/2. Extra-pulmonary hemorrhage (bronchio-pulmonary or central nervous system) was confirmed in 12 grade 1; 3 grade 2; and 2 (3.7%) grade 3 cases.

Outcome measures

Primary endpoint: Response rate (RR): 0 CR/ 21 PR was confirmed in 54 cases, resulting in RR of 38.9% (90% confidence interval [CI], 27.7-51.0% and 95% CI, 25.9-53.1%). Since target-enrollment was not completed, statistical interpretation cannot be concluded. This result was over expected RR, and its effectiveness might be promising. Secondary endpoint: 1. Progression-free survival (PFS): median PFS was 5.2 months (95% CI, 4.2-6.9 months). 2. Overall survival (OS): median OS was 12.7 months (95% CI, 10.2-18.9 month). 3. Disease control rate (DCR): 21 PR/22 SD was confirmed in 54 cases, resulting in DCR of 79.6%.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

12

Month

08

Day

Date of IRB

2018

Year

01

Month

16

Day

Anticipated trial start date

2018

Year

02

Month

05

Day

Last follow-up date

2023

Year

02

Month

04

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

12

Month

27

Day

Last modified on

2024

Year

03

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034942