UMIN-CTR Clinical Trial

Public title

Phase II study of ramucirumab and irinotecan combination therapy as second-line treatment in patients with metastatic or advanced gastric cancer

Acronym

HGCSG 1603

Scientific Title

Phase II study of ramucirumab and irinotecan combination therapy as second-line treatment in patients with metastatic or advanced gastric cancer

Scientific Title:Acronym

HGCSG 1603

Region

Japan

Condition

Gastric Cancer

Classification by specialty

Gastroenterology

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Assessment of the efficacy and safety of ramucirumab and irinotecan combination therapy in metastatic or advanced gastric cancer refractory to initial chemotherapy.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

progression-free survival rate at six months (PFS rate at 6 months)

Key secondary outcomes

overall survival, progression-free survival, response rate, safety, and dose intensity for each drug

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Antitumor agents
Irinotecan
Ramucirumab
every two weeks

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. Confirmed stage IV or recurrent gastric adenocarcinoma that is refractory or intolerant to initial chemotherapy.
2. Age of 20 years or older.
3. ECOG PS scale 0-1.
4. No history of treatment with irinotecan.
5. Confirmation of the progression or recurrence following initial treatment and potential presence of an evaluable lesion less than 28 days before registration using CT or MRI findings, according to RECIST version 1.1. Presence or absence of a measurable lesion is not an inclusion criterion.
6. Last day of initial chemotherapy administration is more than 14 days before registration.
7. Fulfillment of the standards related to major organ functions within 14 days before registration.
8. Patients who are negative for HER-2/neu and those with unknown HER-2/neu status are eligible. HER-2/neu-positive patients are eligible if they received treatments including trastuzumab and if the disease progress is confirmed.
9. Available written informed consent.
10. Have an estimated life expectancy of > 12 weeks in the judgment of the investigator.
11. The patient, if female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate < 1%) during and for 12 weeks after the treatment period.

Key exclusion criteria

1. Major surgery within 28 days before registration.
2. The patient has a history of DVT, PE, or any other significant thromboembolism during the 3 months prior.
3. Administration of anticoagulant therapy such as warfarin and LMWH.
4. The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet agents.
5. Have documented brain metastases, leptomeningeal disease or uncontrolled spinal cord compression.
6. Diagnosis of arterial hypertension that cannot be controlled with standard medical management.
7. The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
8. Primary cancers diagnosed within the previous five years.
9. The patient has symptomatic congestive heart failure or symptomatic or poorly controlled cardiac arrhythmia.
10. The patient has experienced any arterial thrombotic event within 6 months prior.
11. Serious complications or comorbidities.
12. The patient has experienced any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy.
13. History of gastrointestinal perforation and/or fistulae within 6 months prior to registration.
14. Pericardial or pleural effusion or ascites requiring treatment including drainage.
15. Pregnancy, breast-feeding, or plans of pregnancy.
16. Local or systemic active infection requiring treatment; however, HBs-Ag positive patients controlled by nucleic acid analogs and those confirmed as HBV DNA can be enrolled.
17. Current or recent treatment with another investigational drug or participation in another interventional clinical trial.
18. Have known allergy or hypersensitivity to any components of study treatment.
19. The patient has: cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
20. Participation in the clinical trial is determined as unsuitable.

Target sample size

35

Name of lead principal investigator

1st name	Yoshito
Middle name
Last name	Komatsu

Organization

Hokkaido University Hospital

Division name

Division of Cancer Center

Zip code

060-8648

Address

Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido

TEL

011-706-5657

Email

ykomatsu@med.hokudai.ac.jp

Name of contact person

1st name	Yasuyuki
Middle name
Last name	KAWAMOTO

Organization

Hokkaido University Hospital

Division name

Division of Cancer Center

Zip code

060-8648

Address

Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido

TEL

011-706-5657

Homepage URL

Email

y-kawamoto@pop.med.hokudai.ac.jp

Institute

Hokkaido Gastrointestinal Cancer Study Group (HGCSG)

Institute

Department

Personal name

Organization

Eli Lilly Japan K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Clinical Research and Medical Innovation Center, Hokkaido University Hospital

Address

Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido

Tel

0117067636

Email

crjimu@huhp.hokudai.ac.jp

Secondary IDs

YES

Study ID_1

jRCTs011180029

Org. issuing International ID_1

Japan Registry of Clinical Trials

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

12

Month

13

Day

URL releasing protocol

No

Publication of results

Published

URL related to results and publications

https://doi.org/10.1093/oncolo/oyac086

Number of participants that the trial has enrolled

35

Results

Progression-free survival rate at 6 months was 26.5% (95%CI, 13.2-41.8%, P = 0.1353). This study did not meet its primary endpoint.

Results date posted

2022

Year

06

Month

18

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2022

Year

05

Month

17

Day

Baseline Characteristics

Median age was 70 years (range, 47-80 years); male/female: 10/25; ECOG PS 0/1:22/13.
The primary site was the esophagogastric junction in 4 patients and the stomach in 31 patients.
UGT1A1 status were wild-type, 4; *6 or *28 single heterozygous, 13; double variant, 1; and 7 not tested.
Twenty-seven patients had measurable lesion and eight patients did not.
First-line treatment included S-1 + oxaliplatin, 17; Capecitabine + oxaliplatin, 7; FOLFOX, 6; Nab-PTX + S-1 + oxaliplatin, 1; Docetaxel + S-1 + CDDP, 1; S-1 + CDDP, 1; Capecitabine + CDDP, 1; S-1 + docetaxel, 1.
There were 9 and 26 patients with and without prior trastuzumab treatment, respectively.
There were 0 and 35 patients with and without prior ramucirumab treatment, respectively.
Eight patients had a history of gastrectomy and 27 patients had no gastrectomy.

Participant flow

Enrollment speed was somewhat above the original schedule, and enrollment was completed at 1 year and 9 months for a 2-year and 0-month scheduled enrollment period.
Twenty-six patients discontinued study treatment due to disease progression and four discontinued due to adverse events. One patient received curative resection and one continued the study treatment at the data cutoff for analysis.

Adverse events

Adverse events at least Grade 3 included neutropenia 51%, leukopenia 43%, anemia 20%, anorexia 14%, febrile neutropenia 11%, diarrhoea 9%, hypertension 9%, proteinuria 9%, and hypoalbuminemia 9%.
No death or new safety signals with a causal relation to the study treatment were observed.

Outcome measures

Progression-free survival rate at 6 months was 26.5% (95%CI, 13.2-41.8%, P = 0.1353). This study did not meet its primary endpoint.

Plan to share IPD

No

IPD sharing Plan description

There is no plan to share IPD because informed consent has not been obtained from the study subjects for secondary use of the data.

Recruitment status

Completed

Date of protocol fixation

2017

Year

12

Month

20

Day

Date of IRB

2017

Year

12

Month

19

Day

Anticipated trial start date

2017

Year

12

Month

21

Day

Last follow-up date

2020

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

2020

Year

09

Month

30

Day

Date analysis concluded

2021

Year

05

Month

02

Day

Other related information

Registered date

2017

Year

12

Month

13

Day

Last modified on

2022

Year

06

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034675