UMIN-CTR Clinical Trial

Basic information
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
Condition	Gastric Cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	Hokkaido Gastrointestinal Cancer Study Group (HGCSG)
Institute
Department

Funding Source
Organization	Eli Lilly Japan K.K.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
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
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
Institutions

Other administrative information
Date of disclosure of the study information	2017 Year 12 Month 13 Day

Related information
URL releasing protocol	No
Publication of results	Published

Result
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.

Progress
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
Other related information

Management information
Registered date	2017 Year 12 Month 13 Day
Last modified on	2022 Year 06 Month 18 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000034675