UMIN-CTR Clinical Trial

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

<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

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

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
- Overall survival

2) Estimation of effective blood concentration of metformin

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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 corical steroids or immunosuppressive agents within last 3 weeks
22)Patients with history of cancer immunotherapy
23)Radiation therapy within last 4 weeks
24)Patient who have or plan to have live vaccination within last 28 days
25)Pregnant or lactating females, female and male patients who cannot agree to practice the adequate birth control after the consent during the study
26)Serious infection or inflammatory disease
27)Patients with psychosis or dementia to interfere to obtain informed consent appropriately
28)Patients who received a transplantation therapy
29)Patients who have obviously metastasis to central nervous system or pia mater
30)Patients who have tumor originated from central nervous system
31)Any other inadequacy for this study

Target sample size

39

Name of lead principal investigator

1st name	Katsuyuki
Middle name
Last name	Hotta

Organization

Okayama University Hospital

Division name

Center for Innovative Clinical Medicine

Zip code

7008558

Address

2-5-1, Shikata-cho, Kita-Ku, Okayama-city, Okayama 700-8558 Japan

TEL

086-235-6504

Email

khotta@md.okayama-u.ac.jp

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

Institute

Okayama University Hospital
Center for Innovative Clinical Medicine

Institute

Department

Personal name

Organization

Ono Pharmaceutical Co.Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

-

Address

-

Tel

-

Email

-

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2017

Year

07

Month

27

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

41

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

Recruitment status

No longer 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

2025

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

07

Month

27

Day

Last modified on

2023

Year

04

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031915