UMIN-CTR Clinical Trial

Basic information
Public title	Phase 1b investigator initiated trial of combination therapy of Metformin and Nivolumab in participants with advanced or recurrent solid cancer.
Acronym	Phase 1b investigator initiated trial of combination therapy Metformin and Nivolumab in participants with advanced or recurrent solid cancer.
Scientific Title	Phase 1b investigator initiated trial of combination therapy of Metformin and Nivolumab in participants with advanced or recurrent solid cancer.
Scientific Title:Acronym	Phase 1b investigator initiated trial of combination therapy Metformin and Nivolumab in participants with advanced or recurrent solid cancer.
Region	Japan

Condition
Condition	<Stage 1> Advanced or recurrent solid cancer <Stage 2> Advanced or recurrent non-small cell lung cancer, advanced or recurrent thymic epithelial tumor and advanced or recurrent pancreatic cancer
Classification by specialty	Gastroenterology Hepato-biliary-pancreatic medicine Pneumology Hematology and clinical oncology Gastrointestinal surgery Hepato-biliary-pancreatic surgery Chest surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	<Stage 1> To assess safety of the combination therapy and pharmacokinetics property of metformin <Stage 2> To assess safety and preliminary efficacy of the combination therapy
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I

Assessment
Primary outcomes	1) Safety - Maximum tolerant dose (MTD):from first administration to last administration (stage 1 only) - Dose limiting toxicity (DLT): for 4 weeks from first administration (stage 1 only) - Adverse event:from first administration to 30 days after last administration 2) Pharmacokinetics property of metformin: from cycle 1 day8 to a day before cycle 2 day 1
Key secondary outcomes	1) Efficacy - Response rate - Progression-free survival (stage 2 only) 2) Estimation of effective blood concentration of metformin

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Continue to administer Nivolumab and Metformin to a patient until the patient correspond to the withdrawal criteria for individual subjects
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) Stage 1: advanced or recurrent solid cancer which is histologically or cytologiacally confirmed 2) Stage 2: advanced or recurrent non-small cell lung cancer or pancreatic cancer which is histologically or cytologiacally confirmed 3) Patients with tumor progression after the first standard treatment 4) Eastern Cooperative Oncology Group performance status (ECOG PS) is 0 or 1 5) Age: more than 20 years old at the date of informed consent 6) Patients with no serious disorder of major organs (bone marrow, heart, lung, liver, and kidney) 7) Patients with written informed consent 8) Stage 1: patients who have a target lesion or a non-target lesion designated by RECIST version 1.1 9) Stage 2: patients who have a target lesion designated by RECIST version 1.1
Key exclusion criteria	1) Patients with obviously HIV antibody positive 2) Patients with HCV antibody positive 3) Patients with HBs antigen positive, HBc antibody or HBs antibody positive 4) Autoimmune disease 5) Interstitial lung disease, pulmonary fibrosis, or radiation pneumonitis 6) Have a history or complication of TB 7) Lactic acidosis 8) Undergoing artificial dialysis 9) Serious liver dysfunction 10) Dysfunction in cardiovascular or respiratory system, likely to be a hypoxemia 11) Alcohol addict 12) Patients with history of anaphylaxis induced by component of the study drug or biguanide-based medicine 13) Patients with history of serious (Grade 3) anaphylaxis induced by antibody preparation 14) Uncontrollable hypertension 15) Uncontrollable endocrine disease 16) Patients who have active inflammatory bowel disease or other serious GI chronic conditions associated with diarrhea 17) Diabetes 18) Patients who have unstable angina or myocardial infarction 19) Patients with double cancer 20) Patients who had administration of biguanide-based medicine within last a year 21) Patients who have or plan to have administration of other anti-cancer agents, other study drugs, sustained systemic adrenal cortical steroids or immunosuppressive agents within last 3 weeks 22) Patients with history of cancer immunotherapy 23) Radiation therapy within last 4 weeks 24) Pregnant or lactating females, female and male patients who cannot agree to practice the adequate birth control after the consent during the study 25) Serious infection or inflammatory disease 26) Patients with psychosis or dementia to interfere to obtain informed consent appropriately 27) Patients who received a transplantation therapy 28) Patients who have obviously metastasis to central nervous system or pia mater 29) Patients who have tumor originated from central nervous system 30) Any other inadequacy for this study
Target sample size	39

Research contact person
Name of lead principal investigator	1st name Katsuyuki Middle name Last name Kiura
Organization	Okayama University Hospital
Division name	Department of Allergy and Respiratory Medicine
Zip code	7008558
Address	2-5-1, Shikata-cho, Kita-Ku, Okayama-city, Okayama 700-8558 Japan
TEL	086-223-7151
Email	kkiura@md.okayama-u.ac.jp

Public contact
Name of contact person	1st name Tatsushi Middle name Last name Goto
Organization	Fiverings Co.,Ltd.
Division name	Medical team
Zip code	5300044
Address	Urban Ace Higashitenma-BLDG, 1-1-19, Higashitenma,Kita-ku,Osaka 530-0044 Japan
TEL	06-6358-7110
Homepage URL
Email	gotou@fiverings.co.jp

Sponsor
Institute	Okayama University Hospital Department of Allergy and Respiratory Medicine
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	-
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	岡山大学病院（岡山県）、独立行政法人国立病院機構四国がんセンター（愛媛県）

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 27 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	Open public recruiting
Date of protocol fixation	2017 Year 06 Month 15 Day
Date of IRB	2017 Year 07 Month 18 Day
Anticipated trial start date	2017 Year 08 Month 25 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

Other
Other related information

Management information
Registered date	2017 Year 07 Month 27 Day
Last modified on	2019 Year 07 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031915

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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