UMIN-CTR Clinical Trial

Basic information
Public title	A multicenter, phase 1/2 study of Ramucirumab plus Nivolumab as second-line therapy in participants with gastric or GEJ cancer
Acronym	A multicenter, phase 1/2 study of Ramucirumab plus Nivolumab as second-line therapy in participants with gastric or GEJ cancer
Scientific Title	A multicenter, phase 1/2 study of Ramucirumab plus Nivolumab as second-line therapy in participants with gastric or GEJ cancer
Scientific Title:Acronym	A multicenter, phase 1/2 study of Ramucirumab plus Nivolumab as second-line therapy in participants with gastric or GEJ cancer
Region	Japan

Condition
Condition	Advanced or recurrent unresectable gastric or GEJ cancer
Classification by specialty	Gastroenterology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	Phase 1 To estimate maximum tolerated dose (MTD) and dose limiting toxicity (DLT) and to determine of combination therapy of Ramucirumab and Nivolumab and to determine recommended dose (RD) of the therapy. Phase 2 To assess safety and efficacy of the combination therapy.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	Phase 1 Number of participants with dose limiting toxicities (DLTs) for 28 days from first administration Phase 2 Progression free survival rate after 6 months
Key secondary outcomes	Phase 1 Number of participants with adverse events Phase 2 Overall response rate (ORR) Disease control rate (DCR) Progression-free survival (PFS) Overall survival (OS) Number of participants with adverse events

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Phase 1 (Level 1) Ramucirumab: 8 mg/kg, every 2 weeks Nivolumab: 3 mg/kg, every 2 weeks
Interventions/Control_2	Phase 1 (Level 0) Ramucirumab: 8 mg/kg, every 2 weeks Nivolumab: 1 mg/kg, every 2 weeks
Interventions/Control_3	Phase 2 Ramucirumab: 8 mg/kg, every 2 weeks Nivolumab: recommended dose established in the phase 1 (3 mg/kg or 1 mg/kg), every 2 weeks
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	- Advanced or recurrent unresectable gastric or GEJ cancer - Histologically confirmed adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma or poorly differentiated adenocarcinoma), signet-ring cell carcinoma, mucinous adenocarcinoma or hepatoid adnocarcinoma - Patients with normal oral intake - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Patients who have measurable target lesion - Patients has a refractory or intolerant pretreatment by pyrimidine fluoride anticancer agent and platinum-based anticancer agent - Patients with no pretreatment history including ramucirumab, nivolumab or other therapies targeting control of T cells - Patients with written informed consent
Key exclusion criteria	- Patients have double cancer - Patients have infection required systemic therapy - Known central nervous system (CNS) metastasis - Patients with history of pneumonitis or pulmonary fibrosis - Patients with history of serious anaphylaxis induced by antibody preparation - Patients who have known active autoimmune disease or history of chronic recurrent autoimmune disease - Female who is pregnant, lactating or suspected pregnancy - Patients with psychosis or dementia to interfere to obtain informed consent appropriately
Target sample size	44

Research contact person
Name of lead principal investigator	1st name Ken Middle name Last name Kato
Organization	National Cancer Center Japan Hospital
Division name	Department of Head and Neck, Esophageal Medical Oncology
Zip code	104-0045
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
TEL	03-3542-2511
Email	kenkato@ncc.go.jp

Public contact
Name of contact person	1st name Hirokazu Middle name Last name Shoji
Organization	National Cancer Center Japan Hospital
Division name	Department of Gastrointestinal Medical Oncology
Zip code	104-0045
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
TEL	03-3542-2511
Homepage URL
Email	hshouji@ncc.go.jp

Sponsor
Institute	Department of Head and Neck Oncology, National Cancer Center Japan Hospital
Institute
Department

Funding Source
Organization	Ono Pharmaceutical Co. Ltd.
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	Institutional Review Board of National Cancer Center
Address	5-1-1, Thukiji, Chuo-ku, Tokyo, 104-0045, Japan
Tel	03-3542-2511
Email	NCC_IRBoffice@ml.res.ncc.go.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT02999295
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	国立研究開発法人国立がん研究センター中央病院（東京都）、公益財団法人 がん研究会有明病院（東京都）、埼玉県立がんセンター（埼玉県）、静岡県立静岡がんセンター（静岡県）、独立行政法人国立病院機構 九州がんセンター（福岡県）

Other administrative information
Date of disclosure of the study information	2017 Year 01 Month 06 Day

Related information
URL releasing protocol	https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.129
Publication of results	Published

Result
URL related to results and publications	https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.129
Number of participants that the trial has enrolled	46
Results	46 advanced gastric cancer patients (median age 66 years) were enrolled. No dose limiting toxicities were observed in the phase 1 part. With median follow up time of 10.2 month, 6-month progression free survival rate was 37.4% (90% confidential intervals: 25.7-49.2%), which met the primary endpoint of the phase 2 part. objective responce rate/disease responce rate were 26.7%/62.2%. Median progression free survival/overall survival were 2.9/9.0 months.
Results date posted	2022 Year 11 Month 28 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Advanced gastric cancer patients with disease progression on first line chemotherapy containing platinum
Participant flow	Patients received Nivolumab (3mg/kg, Q2W) and Ramcirumab (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase 1 part), additional 40 patients were required in a phase 2 part.
Adverse events	Grade 3 or 4 treatment related adverse events were hypertension (n=2), diarrhea (n=2), perforation at jejunum (n=1), hemorrhage (n=1), colitis (n=1), pancreatitis (n=1), liver dysfunction (n=1), cholangitis (n=1), hematoma (n=1), neutropenia (n=1) and proteinuria (n=1). There were no treatment-related deaths.
Outcome measures	Primary analysis: 6-months progression-free survival rate Secondary endpoints: Objective response rate, Disease control rate, Progression free survival, Overall survival, Safety
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 11 Month 04 Day
Date of IRB	2016 Year 12 Month 07 Day
Anticipated trial start date	2017 Year 01 Month 12 Day
Last follow-up date	2020 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2022 Year 03 Month 31 Day

Other
Other related information

Management information
Registered date	2017 Year 01 Month 06 Day
Last modified on	2022 Year 11 Month 28 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029360