UMIN-CTR Clinical Trial

Basic information
Public title	An open label, non-randomized phase I/II study of ramucirumab in combination with nab-paclitaxel as second-line therapy in patients with advanced gastric cancer
Acronym	A phase I/II study of ramucirumab plus nab-paclitaxel as second-line therapy in patients with advanced gastric cancer
Scientific Title	An open label, non-randomized phase I/II study of ramucirumab in combination with nab-paclitaxel as second-line therapy in patients with advanced gastric cancer
Scientific Title:Acronym	A phase I/II study of ramucirumab plus nab-paclitaxel as second-line therapy in patients with advanced gastric cancer
Region	Japan

Condition
Condition	gastric cancer
Classification by specialty	Gastroenterology Hematology and clinical oncology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Phase I part: To determine the maximum tolerated dose (MTD) and recommended dose (RD)of ramucirumab plus nab-PTX in patients with advanced gastric cancer. Phase II part: To evaluate the efficacy and safety of ramucirumab plus nab-PTX.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Phase I part primary endpoint: The frequency of Dose limiting toxicity(DLT) Phase II part primary endpoint: Overall response rate
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Ramucirumab: 8mg/kg(i.v.) administration at day 1,15,29 Nab-Paclitaxel: 180-260mg/m2 administration at day 1,22 (dose escalation: level1= 180mg/m2,level 2 = 220mg/m2, level 3 = 260mg/m2)
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	75 years-old >
Gender	Male and Female
Key inclusion criteria	1. Age over 20 years old and under 75 years old 2.Histological confirmed unresectable advanced or recurrent gastric cancer 3. Refractory to fluoropyrimidine and platinum containing chemotherapy. Within 4 months after last chemotherapy. 4. ECOG performance status 0-1 5. Cases with measurable lesion 6. No adverse event over Grade2(NCI-CTCAE, Ver 4.02) attributable to prior surgery or chemotherapy 7. Peripheral sensory neuropathy<=Grade1 8. No prior therapy with paclitaxel 9. Cases with adequately maintained organ functions and fullfilling the following conditions within 2 weeks before registration. a)leukocyte count <= 12000/mm3 b)neutrophil count >= 2000/ mm3 c)hemoglobin level >= 9.0g/ dL d)platelet count >= 100,000/mm3 e)AST and ALT <=100IU/L, or AST and ALT <=200IU/L with liver metastases f)total bilirbin < 1.5mg/dL g)ALP<=2.5xULN in each institution h)serum creatinine <=1.5xULN in each institution or creatinine clearance=>50ml/min i)PT-INR<1.5 or PT<1.5xULN in each institution j)APTT<=1.5xULN in each institution k)Urinary protein is<1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria more than 2+, then a 24-hour must demonstrate<1000 mg of protein in 24 hours. 10.Cases expected to survive for 90 days or more 11.Written informed consent
Key exclusion criteria	1. History of severe drug allergy or hypersensitivity 2. Active or uncontrolled clinically serious infection 3. Evidence of any other serious disease 4. Synchronous or metachronous malignancies other than carcinoma in situ or mucosal carcinoma 5. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant) during the 3 months prior to randomization. 6. Receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. 7. Receiving chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet agents. Aspirin use at doses up to 325 mg/day is permitted. 8. Significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry. 9. History of gastrointestinal perforation and/or fistulae within 6 months prior to randomization. 10. Symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia. 11. Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. 12. Uncontrolled arterial hypertension >150/>90mmHg despite standard medical management 13. Serious or non healing wound or peptic ulcer or bone fracture within 28 days prior to randomization 14. Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohns disease, ulcerative colitis, or chronic diarrhea 15.Massive ascites, pleural effusion, or cardiac effusion 16.The patient is pregnant or breastfeeding 17. Judged inappropriate by the investigators
Target sample size	68

Research contact person
Name of lead principal investigator	1st name Middle name Last name Sachio Fushida
Organization	Digestive Disease Support Organization (DDSO)
Division name	Gastroenterologic surgery
Zip code
Address	35-1, Yonemaru-machi, Kanazawa, Ishikawa 921-8004, Japan
TEL	076-265-2000
Email	junkino0416@gmail.com

Public contact
Name of contact person	1st name Middle name Last name Jun Kinoshita
Organization	Digestive Disease Support Organization (DDSO)
Division name	Gastroenterologic surgery
Zip code
Address	35-1, Yonemaru-machi, Kanazawa, Ishikawa 921-8004, Japan
TEL	076-265-2000
Homepage URL
Email	junkino0416@gmail.com

Sponsor
Institute	Digestive Disease Support Organization (DDSO)
Institute
Department

Funding Source
Organization	Digestive Disease Support Organization (DDSO)
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 01 Month 15 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Terminated
Date of protocol fixation	2015 Year 12 Month 28 Day
Date of IRB	2015 Year 10 Month 01 Day
Anticipated trial start date	2016 Year 01 Month 15 Day
Last follow-up date	2018 Year 06 Month 28 Day
Date of closure to data entry	2018 Year 06 Month 28 Day
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 01 Month 15 Day
Last modified on	2019 Year 07 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000023554