Checkpoint Inhibitor and Radiotherapy for Recurrent Gastric Cancer (CIRCUIT)

NCT03453164 | Completed Phase 1 Results

• 1 other identifier: RK29040
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims 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).

Conditions

Gastric Cancer

Keywords

Radiotherapy; anti-PD-1 antibody

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  Analysis item: Disease control rate of non-irradiated target lesions. The rate of patients with a best overall response of stable disease (SD) or better confirmed by 180 days, starting from the start date of radiotherapy. The RECIST Guidelines Version 1.1 was used to determine overall response such as complete response (CR), partial response (PR), SD, and progressive disease (PD) at each imaging time. If imaging is not available, the patient is considered deficient (NE).

  6 months

Secondary Outcomes (3)

• Median Survival Time

  From the start date of radiotherapy until the date of death from any cause or date of last documented survival, assessed up to approximately 31 months.

• Safety (Grade and Frequency of Adverse Events)

  Adverse events were monitored from the start date of radiotherapy until the end of study protocol or death from any cause, and were assessed up to approximately 6 months. All-Cause Mortality was assessed up to approximately 31 months.

• Local Control Rate

  6 months

Study Arms (1)

Radiotherapy + Nivolumab

EXPERIMENTAL

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) or 240 mg/body, every 2 weeks to a total of 6 courses)

Radiation: Radiotherapy; Drug: Nivolumab

Interventions

Radiotherapy RADIATION

Radiotherapy of 22.5 Gy/5 fractions/5 days was given to a symptomatic lesion or the largest asymptomatic lesion suitable for irradiation from Day 1.

Radiotherapy + Nivolumab

Nivolumab DRUG

Nivolumab was administered intravenously starting on Day 15-22 at a dose of 3 mg/kg (body weight) or 240 mg/body every 2 weeks to a total of 6 courses of administration.

Also known as: Opdivo

Radiotherapy + Nivolumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unresectable advance or recurrent GC with intolerance or progression 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: WBC ≥3000/μl, neutrophil ≥1500/μl, hemoglobin ≥9.0g/dl, platelets ≥100,000/μl, 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.
• Expected survival \>=3 months.
• Written informed consent is obtained from the patient prior to study enrollment.

You may not qualify if:

• No tumor lesions that can be irradiated.
• Metachronous and simultaneous overlapping cancers (excluding intraepithelial cancer of the uterine cervix, fully treated basal cell carcinoma of the skin, and malignant tumors that were treated more than 5 years ago and have not recurred).
• A history of severe hypersensitivity reactions to other Ab products.
• Taking immunosuppressive drugs or corticosteroids (prednisone or prednisolone equivalent ≥ 15 mg/day).
• Active autoimmune diseases or a history of recurrent autoimmune diseases (patients with type-1 diabetes, hypothyroid controllable by hormone replacement therapy, and dermatosis without the need for systemic therapy are eligible).
• Complications or history of interstitial pneumonia or pulmonary fibrosis diagnosed by imaging studies or clinical findings.
• Presence of severe disease or medical conditions: severe nutritional deficiencies, transient ischemic attack within 180 days prior to enrollment, cerebral vascular attack within 180 days prior to enrollment, thrombus or thromboembolism within 180 days prior to enrollment, congestive heart failure (NYHA class III or IV), unstable angina, myocardial infarction within 12 months, severe arrhythmias requiring medication, conduction abnormalities such as AV block beyond the second degree, uncontrollable hypertension, liver cirrhosis (Child Class B or higher), mental disorders that may interfere with compliance with this study protocol, unstable diabetes, uncontrolled pericardial fluid, uncontrolled ascites, uncontrolled pleural effusions, diseases requiring anticoagulation therapy (excluding antiplatelet therapy including low-dose aspirin), and systemic infection with treatment.
• Pregnant or lactating female.
• Fertile female who are unwilling to use contraception.
• Fertile male who are not willing to use contraception during study drug administration and for 7 months after study completion (if the partners are fertile females).
• Prohibited previous treatment: within 56 days of registration; radioactive drugs (except radiopharmaceuticals for examination or diagnostic purposes), within 28 days of registration; corticosteroids (excluding temporary use and predonine or prednisolone equivalent ≤15 mg/day), immunosuppressant drugs, anti-cancer drugs, adhesive treatment of pleura or pericardium, surgery with general anesthesia, and unapproved drugs, within 14 days of registration; surgery with local or superficial anesthesia.
• Participating in other clinical trials or clinical studies (excludes those without intervention).
• A positive HIV antigen/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 drug therapies for T-cell regulation.
• Determined by the investigator to be ineligible for participation in this study.

Sponsors & Collaborators

• Fukushima Medical University: lead

Study Sites (1)

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

Location

Related Publications (5)

• Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, Murata K, Fujii H, Nakano T, Kono K. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 2012 Aug 15;72(16):3967-76. doi: 10.1158/0008-5472.CAN-12-0851. Epub 2012 Jun 14.

  PMID: 22700877 BACKGROUND

• Yoshimoto Y, Suzuki Y, Mimura K, Ando K, Oike T, Sato H, Okonogi N, Maruyama T, Izawa S, Noda SE, Fujii H, Kono K, Nakano T. Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model. PLoS One. 2014 Mar 31;9(3):e92572. doi: 10.1371/journal.pone.0092572. eCollection 2014.

  PMID: 24686897 BACKGROUND

• Sato H, Suzuki Y, Yoshimoto Y, Noda SE, Murata K, Takakusagi Y, Okazaki A, Sekihara T, Nakano T. An abscopal effect in a case of concomitant treatment of locally and peritoneally recurrent gastric cancer using adoptive T-cell immunotherapy and radiotherapy. Clin Case Rep. 2017 Feb 15;5(4):380-384. doi: 10.1002/ccr3.758. eCollection 2017 Apr.

  PMID: 28396751 BACKGROUND

• Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6.

  PMID: 28993052 BACKGROUND

• Mimura K, Ogata T, Nguyen PHD, Roy S, Kared H, Yuan YC, Fehlings M, Yoshimoto Y, Yoshida D, Nakajima S, Sato H, Machida N, Yamada T, Watanabe Y, Tamaki T, Fujikawa H, Inokuchi Y, Hayase S, Hanayama H, Saze Z, Katoh H, Takahashi F, Oshima T, Goel A, Nardin A, Suzuki Y, Kono K. Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer. J Immunother Cancer. 2024 Jan 30;12(1):e008385. doi: 10.1136/jitc-2023-008385.

  PMID: 38290769 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Radiotherapy; Nivolumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Prof. Koji Kono
• Organization: Fukushima medical university of medicine

kojikono@fmu.ac.jp

+81245471259

Study Officials

• Koji Kono, Professor

  Fukushima Medical University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 21, 2018
• First Posted: March 5, 2018
• Study Start: March 28, 2018
• Primary Completion: January 7, 2021
• Study Completion: January 31, 2021
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)