Checkpoint Inhibitor and Radiotherapy for Recurrent Gastric Cancer (CIRCUIT)
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|ClinicalTrials.gov Identifier: NCT03453164|
Recruitment Status : Unknown
Verified July 2020 by Koji Kono, Fukushima Medical University.
Recruitment status was: Active, not recruiting
First Posted : March 5, 2018
Last Update Posted : July 15, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Gastric Cancer||Radiation: Radiotherapy + Nivolumab||Phase 1 Phase 2|
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), localized short-term radiotherapy of 22.5 Gy/5 fractions/5 days will be applied to a symptomatic lesion or the largest asymptomatic lesion suitable for irradiation (Day 1-5). Nivolumab will be administered starting from Day 15-22 at a dose of 3 mg/kg (body wait) every 2 weeks to a total of 6 courses (end of intervention).
The patients will be observed up to Day 180±14 and evaluated on Day 180±14 (end of study).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Combination of Checkpoint Inhibitor and Radiotherapy for Recurrent Gastric Cancer After Initial Treatment With Standard Therapy (CIRCUIT).|
|Actual Study Start Date :||March 28, 2018|
|Estimated Primary Completion Date :||January 14, 2021|
|Estimated Study Completion Date :||February 28, 2021|
Experimental: Radiotherapy + Nivolumab
Localized short-term radiotherapy (22.5 Gy/5 fractions/5 days, Day 1-5) + nivolumab (starting on Day 15-22, a dose of 3 mg/kg (body weight), every 2 weeks to a total of 6 courses)
Radiation: Radiotherapy + Nivolumab
Radiotherapy of 22.5 Gy/5 fractions/5 days will be given to a symptomatic lesion or the largest asymptomatic lesion suitable for irradiation from Day 1. Nivolumab will be administered intravenously starting on Day 15-22 at a dose of 3 mg/kg (body weight) every 2 weeks to a total of 6 courses of administration.
Other Name: Nivolumab
- Disease control rate [ Time Frame: 6 months ]Tumor growth (PD) in CT (MRI possible) or PET-CT, in comparison to the images at study entry will be "non-control", and evaluation of CR/PR/SD will be "control".
- Median survival time [ Time Frame: 6 months ]Median value of survival time in full analysis set.
- Incidence of treatment-emergent adverse events [ Time Frame: 6 months ]The frequency of adverse events according to the grades based on CTCAE ver. 4.0. will be evaluated.
- Local control rate [ Time Frame: 6 months ]Tumor growth (PD) in CT (MRI possible) or PET-CT, in comparison to the images at study entry will be "non-control", and evaluation of CR/PR/SD will be "control".
- Expression of PD-L1 and MHC class I on tumor cells, number of CD8 positive lymphocytes in tumor microenvironment [ Time Frame: 6 months ]The evaluation of PD-L1 and MHC class I expression on tumor cells, and the number of CD8 positive lymphocytes in tumor microenvironment will be conducted by immunohistochemistry only for participants with available samples.
- Peak plasma cytokine concentration [ Time Frame: At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months. ]HMGB-1, IL-1β, IL-10, IFN-γ in plasma will be measured by ELISA. Measurement will be performed at different time points.
- Peak regulatory T-cell population [ Time Frame: At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months. ]The rate of regulatory T-cell population in peripheral blood will be evaluated by flow cytometry. Measurement will be performed at different time points.
- Peak antigen-specific cytotoxic T lymphocyte population [ Time Frame: At the time of registration, 2 weeks, 6 weeks, 10 weeks, and 6 months. ]The rate of antigen-specific cytotoxic T lymphocyte in peripheral blood will be evaluated by flow cytometry. Measurement will be performed at different time points.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||20 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Unresectable recurrent gastric cancer with progression (intolerance or PD) after standard treatment (primary and secondary chemotherapy).
- 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.
- Age: 20 =<
- ECOG performance status (PS): 0-2
- No contraindication for nivolumab (anti-PD-1 antibody) administration.
- No contraindication for radiotherapy.
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)]
- Expected survival >=3 months.
- Written informed consent obtained before entry to the study.
- No tumor lesions to be irradiated.
- 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).
- Past severe hypersensitive reaction to antibody (Ab) drugs.
- Use of immunosuppressant drugs or adrenocortical hormone (predonine or prednisolone (PDN/PSL) equivalent >=15 mg/day).
- 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.
- History of interstitial pneumonia or pulmonary fibrosis diagnosed with imaging studies (CT is preferred) or clinical findings.
- Presence of severe disease or pathology.
- Pts during pregnancy or lactation.
- Fertile female pts w/o intention to practice contraception.
- Fertile male pts w/o intention to practice contraception during and for 7 months after the study, if the partners are fertile females.
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.
- Concurrent participation in other clinical trials/studies (excludes those w/o intervention).
- Positivity in HIV-1 Ab test, HIV-2 Ab test, or HTLV-1 Ab test.
- 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.
- Pts whom the physicians in the study consider inappropriate for entry.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03453164
|Fukushima Medical University Hospital|
|Fukushima, Japan, 960-1295|
|Principal Investigator:||Koji Kono, Professor||Fukushima Medical University Hospital|
Documents provided by Koji Kono, Fukushima Medical University:
|Responsible Party:||Koji Kono, Professor, Fukushima Medical University|
|Other Study ID Numbers:||
|First Posted:||March 5, 2018 Key Record Dates|
|Last Update Posted:||July 15, 2020|
|Last Verified:||July 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action