UMIN-CTR Clinical Trial

Basic information
Public title	Combination of checkpoint inhibitor and radiotherapy for recurrent gastric cancer after initial treatment with standard therapy.
Acronym	CIRCUIT
Scientific Title	Combination of checkpoint inhibitor and radiotherapy for recurrent gastric cancer after initial treatment with standard therapy.
Scientific Title:Acronym	CIRCUIT
Region	Japan

Condition
Condition	Gastric cancer
Classification by specialty	Gastrointestinal surgery Radiology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate safety and efficacy of nivolumab (anti-PD-1 antibody), which is approved as tertiary therapy, and neoadjuvant short-term limited local radiotherapy in patients with unresectable recurrent gastric cancer who progressed (intolerance or PD) after standard treatment (primary and secondary chemotherapy) and have more than one lesion assessable in diagnostic imaging (one lesion must be >=2cm).
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Disease control rate (6 months)
Key secondary outcomes	1) Median survival time (6 months) 2) Incidence of treatment-emergent adverse events (6 months) 3) Local control rate (6 months) 4) Expression of PD-L1 and MHC class I on tumor cells, number of CD8 positive lymphocytes in tumor microenvironment (These will be conducted by immunohistochemistry only for participants with available samples.) 5) Peak plasma HMGB-1, IL-1beta, IL-10, IFN-gamma concentration (At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months) 6) The rate of regulatory T-cell population in peripheral blood (At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months) 7) The rate of antigen-specific cytotoxic T lymphocyte in peripheral blood (At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	No need to know

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Other
Interventions/Control_1	Radiotherapy before administration of nivolumab Dose: 22.5 Gy/5 fractions/5 days
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) Unresectable recurrent gastric cancer with progression (intolerance or PD) after standard treatment (primary and secondary chemotherapy). 2) More than one measurable lesion defined by RECIST guideline version 1.1 in diagnostic imaging (whole-body contrast-enhanced CT or PET-CT) within 14 days before entry, with at least one lesion >=2 cm. 3) Age: 20 =< 4) ECOG performance status (PS): 0-2 5) No contraindication for nivolumab (anti-PD-1 antibody) administration. 6) No contraindication for radiotherapy. 7) The most recent laboratory results within 14 days before study entry fulfill the following. However, if the laboratory results for study entry do not fall within 7 days before the first administration of nivolumab, the blood test must be performed again within 7 days before the administration to check if the results fulfill the following. The use of G-CSF or blood transfusion within 14 days before the laboratory testing is not allowed. WBC >=3000/micro liter(ul), neutrophil >=1500/ul, hemoglobin >=9.0g/dl, platelets >=100,000/ul, total bilirubin <=2.0 times the institutional standard upper limit (ISUL), AST (GOT) and ALT (GPT) <=3.0 times ISUL (in case with liver metastasis, <=5.0 times ISUL), serum creatinine <=1.5 times ISUL or creatinine clearance >=60 ml/min calculated with Cockcroft-Gault equation. Male Ccr = [(140-age)*body weight(kg)]/[72*serum creatinine(mg/dl)] Female Ccr = 0.85*[(140-age)*body weight(kg)]/[72*serum creatinine(mg/dl)] 8) Expected survival >=3 months. 9) Written informed consent obtained before entry to the study.
Key exclusion criteria	1) No tumor lesions to be irradiated. 2) History of other cancers (intraepithelial cancer of uterine cervix, fully treated basal cell carcinoma of skin, malignant tumors treated before >=5 yrs and w/o recurrence are excluded). 3) Past severe hypersensitive reaction to antibody (Ab) drugs. 4) Use of immunosuppressant drugs or adrenocortical hormone (predonine or prednisolone (PDN/PSL) equivalent >=15 mg/day). 5) Active autoimmune diseases or history of recurrent autoimmune diseases. Patients (Pts) with type-1 diabetes, hypothyroid controlled with hormone replacement therapy, dermatosis without need for systemic therapy (for example, vitiligo, psoriasis, alopecia) are eligible. 6) History of interstitial pneumonia or pulmonary fibrosis diagnosed with imaging studies (CT is preferred) or clinical findings. 7) Presence of severe disease or pathology. 8) Pts during pregnancy or lactation. 9) Fertile female pts w/o intention to practice contraception. 10) Fertile male pts w/o intention to practice contraception during and for 7 months after the study, if the partners are fertile females. 11) Prohibited pre-treatment. Within 56 days before entry: radioactive drugs (exclude those intended for testing or diagnosis) Within 28 days before entry: systemic adrenocortical hormone (excludes temporary use or PDN/PSL equivalent of <15 mg/day), immunosuppressant drugs, anti-cancer drugs, adhesive treatment of pleura or pericardium, surgery with general anesthesia, use of unapproved drugs. Within 14 days before entry: surgery with local or superficial anesthesia. 12) Concurrent participation in other clinical trials/studies (excludes those w/o intervention). 13) Positivity in HIV-1 Ab test, HIV-2 Ab test, or HTLV-1 Ab test. 14) History of treatment using ONO-4538, anti-PD-1 Ab, anti-PD-L1 Ab, anti-PD-L2 Ab, anti-CD137 Ab, anti-CTLA-4 Ab, or other Ab or drugs intended for T-cell regulation. 15) Pts whom the physicians in the study consider inappropriate for entry.
Target sample size	40

Research contact person
Name of lead principal investigator	1st name Koji Middle name Last name Kono
Organization	Fukushima Medical University Hospital
Division name	Department of Gastrointestinal Tract Surgery
Zip code	960-1295
Address	1 Hikarigaoka, Fukushima, Fukushima
TEL	024-547-1111
Email	kojikono@fmu.ac.jp

Public contact
Name of contact person	1st name Kosaku Middle name Last name Mimura
Organization	Fukushima Medical University Hospital
Division name	Department of Gastrointestinal Tract Surgery
Zip code	960-1295
Address	1 Hikarigaoka, Fukushima, Fukushima
TEL	024-547-1111
Homepage URL
Email	kmimura@fmu.ac.jp

Sponsor
Institute	Fukushima Medical University
Institute
Department

Funding Source
Organization	Ono Pharmaceutical Co.,ltd. Bristol-Myers Squibb Company
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Fukushima Medical University
Address	1 Hikarigaoka, Fukushima, Fukushima
Tel	024-547-1111
Email	c-kiban@fmu.ac.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT03453164
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	福島県立医科大学附属病院（福島県）

Other administrative information
Date of disclosure of the study information	2018 Year 03 Month 01 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	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

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 01 Month 19 Day
Date of IRB	2018 Year 11 Month 16 Day
Anticipated trial start date	2018 Year 03 Month 01 Day
Last follow-up date	2021 Year 01 Month 31 Day
Date of closure to data entry
Date trial data considered complete	2021 Year 01 Month 31 Day
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 02 Month 28 Day
Last modified on	2021 Year 08 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035376