Trial Outcomes & Findings for Checkpoint Inhibitor and Radiotherapy for Recurrent Gastric Cancer (CIRCUIT) (NCT NCT03453164)

Last Updated: 2024-09-19

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

41 participants

Primary outcome timeframe

6 months

Results posted on

2024-09-19

Participant Flow

Participant milestones

Participant milestones
Measure	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) or 240 mg/body, every 2 weeks to a total of 6 courses) 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. 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.
Overall Study STARTED	41
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	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) or 240 mg/body, every 2 weeks to a total of 6 courses) 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. 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.
Overall Study Lack of Efficacy	16
Overall Study 3 cases did not meet the criteria for nivolumab initiation.	3

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiotherapy + Nivolumab n=41 Participants 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) 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. 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.
Age, Continuous	70 years n=41 Participants
Sex: Female, Male Female	7 Participants n=41 Participants
Sex: Female, Male Male	34 Participants n=41 Participants
Eligible patients	40 Participants n=41 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Since one patient whose target lesions did not meet the selection criteria for this study according to the RECIST guideline version 1.1 was ineligible and was excluded from the efficacy analysis, 40 patients were included in the efficacy analysis.

Outcome measures

Outcome measures
Measure	Radiotherapy + Nivolumab n=40 Participants Single arm study: 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).
Disease Control Rate	9 Participants

SECONDARY outcome

Timeframe: 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.

Overall survival is defined as the period from the start date of radiotherapy until the date of death from any cause or date of last documented survival. In surviving cases, the last date of confirmation of survival is the date of termination. Untraceable cases are terminated on the last date of confirmed survival before the loss of follow-up. At the end of the study period, all enrolled cases are confirmed alive.

Outcome measures

Outcome measures
Measure	Radiotherapy + Nivolumab n=40 Participants Single arm study: 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).
Median Survival Time	230 Days Interval 157.0 to 330.0

SECONDARY outcome

Timeframe: 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.

Population: The frequency and rate of grade 3 or higher adverse events.

The frequency of adverse events from all enrolled cases is tabulated by adverse event name and worst grade according to CTCAE ver.4.0. All adverse events are summarized without regard to causal relationships to the study treatment. The frequency and rate of grade 3 or higher adverse events are calculated.

Outcome measures

Outcome measures
Measure	Radiotherapy + Nivolumab n=41 Participants Single arm study: 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).
Safety (Grade and Frequency of Adverse Events) Dyspnea	1 Participants
Safety (Grade and Frequency of Adverse Events) Febrile neutropenia	1 Participants
Safety (Grade and Frequency of Adverse Events) Fever	1 Participants
Safety (Grade and Frequency of Adverse Events) Gastric hemorrhage	1 Participants
Safety (Grade and Frequency of Adverse Events) Hyperglycemia	1 Participants
Safety (Grade and Frequency of Adverse Events) Ileus	1 Participants
Safety (Grade and Frequency of Adverse Events) Platelet count decreased	1 Participants
Safety (Grade and Frequency of Adverse Events) Proteinuria	1 Participants
Safety (Grade and Frequency of Adverse Events) Blood bilirubin increased	1 Participants
Safety (Grade and Frequency of Adverse Events) Cholecystitis	1 Participants
Safety (Grade and Frequency of Adverse Events) Hyperkalemia	1 Participants
Safety (Grade and Frequency of Adverse Events) Hyperuricemia	1 Participants
Safety (Grade and Frequency of Adverse Events) Hypoalbuminemia	1 Participants
Safety (Grade and Frequency of Adverse Events) Hyponatremia	1 Participants
Safety (Grade and Frequency of Adverse Events) Anemia	8 Participants
Safety (Grade and Frequency of Adverse Events) Anorexia	5 Participants
Safety (Grade and Frequency of Adverse Events) Tumor pain	3 Participants
Safety (Grade and Frequency of Adverse Events) Dehydration	2 Participants
Safety (Grade and Frequency of Adverse Events) Nausea	2 Participants
Safety (Grade and Frequency of Adverse Events) Alkaline phosphatase increased	1 Participants
Safety (Grade and Frequency of Adverse Events) Supraventricular tachycardia	1 Participants
Safety (Grade and Frequency of Adverse Events) White blood cell decreased	1 Participants
Safety (Grade and Frequency of Adverse Events) Lung infection	1 Participants

SECONDARY outcome

Timeframe: 6 months

Analysis item: Disease control rate of irradiated target lesions. The rate of patients with a best overall response of 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 CR, PR, SD, and PD at each imaging time. If imaging is not available, the patient is considered NE.

Outcome measures

Outcome measures
Measure	Radiotherapy + Nivolumab n=40 Participants Single arm study: 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).
Local Control Rate	16 Participants

Adverse Events

Radiotherapy + Nivolumab

Serious events: 16 serious events

Other events: 19 other events

Deaths: 28 deaths

Serious adverse events

Serious adverse events
Measure	Radiotherapy + Nivolumab n=41 participants at risk Single arm study: 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).
Blood and lymphatic system disorders Anemia	19.5% 8/41 • 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.
Metabolism and nutrition disorders Anorexia	12.2% 5/41 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	7.3% 3/41 • 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.
Metabolism and nutrition disorders Dehydration	4.9% 2/41 • 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.
Gastrointestinal disorders Nausea	4.9% 2/41 • 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.
Investigations Alkaline phosphatase increased	2.4% 1/41 • 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.
Investigations Blood bilirubin increased	2.4% 1/41 • 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.
Hepatobiliary disorders Cholecystitis	2.4% 1/41 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.4% 1/41 • 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.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 1/41 • 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.
General disorders Fever	2.4% 1/41 • 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.
Gastrointestinal disorders Gastric hemorrhage	2.4% 1/41 • 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.
Metabolism and nutrition disorders Hyperglycemia	2.4% 1/41 • 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.
Metabolism and nutrition disorders Hyperkalemia	2.4% 1/41 • 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.
Metabolism and nutrition disorders Hyperuricemia	2.4% 1/41 • 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.
Metabolism and nutrition disorders Hypoalbuminemia	2.4% 1/41 • 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.
Metabolism and nutrition disorders Hyponatremia	2.4% 1/41 • 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.
Gastrointestinal disorders Ileus	2.4% 1/41 • 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.
Investigations Platelet count decreased	2.4% 1/41 • 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.
Renal and urinary disorders Proteinuria	2.4% 1/41 • 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.
Cardiac disorders Supraventricular tachycardia	2.4% 1/41 • 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.
Investigations White blood cell decreased	2.4% 1/41 • 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.
Infections and infestations Lung infection	2.4% 1/41 • 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.

Other adverse events

Other adverse events
Measure	Radiotherapy + Nivolumab n=41 participants at risk Single arm study: 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).
General disorders Fatigue	22.0% 9/41 • 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.
Investigations Aspartate aminotransferase increased	19.5% 8/41 • 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.
Metabolism and nutrition disorders Hypocalcemia	19.5% 8/41 • 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.
Skin and subcutaneous tissue disorders Pruritus	14.6% 6/41 • 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.
Gastrointestinal disorders Vomiting	14.6% 6/41 • 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.
Investigations Alanine aminotransferase increased	12.2% 5/41 • 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.
Gastrointestinal disorders Constipation	12.2% 5/41 • 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.
General disorders Edema limbs	12.2% 5/41 • 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.
Nervous system disorders Peripheral sensory neuropathy	12.2% 5/41 • 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.
Investigations Creatinine increased	9.8% 4/41 • 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.
Vascular disorders Hypertension	9.8% 4/41 • 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.
Gastrointestinal disorders Diarrhea	7.3% 3/41 • 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.

Additional Information

Prof. Koji Kono

Fukushima medical university of medicine

Phone: +81245471259

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place