Gastric cancer S-1 dose optimization study

JRCT ID: jRCTs031230127

Registered date:08/06/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HER2-negative unresectable or advanced recurrent gastric cancer
• Date of first enrollment: 18/08/2023
• Target sample size: 20
• Study type: Interventional
• Intervention(s): S-1 administration along with adjustments based on BBT formula in SOX + NIVO therapy

Outcome(s)

Primary Outcome

1) Safety confirmation part
The safety confirmation part will be conducted in the initial 6 patients to evaluate the incidence of dose-limiting toxic DLTs.

2) Expansion part
The response rate and survival will be evaluated in all patients, including the 6 patients in the safety confirmation part, by adding additional patients as part of the Phase II single-arm study.

Secondary Outcome

Adverse Event Incidence Ratio
Relative drug strength of S-1, oxaliplatin, and nivolumab
Response rate in patients with measurable disease
Disease control rate in patients with measurable disease
Progression-free survival
Overall survival

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) histologically diagnosed as HER2-negative adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma), ring cell carcinoma, mucous carcinoma.
No prior chemotherapy for gastric cancer. Patients with recurrent cancer after 180 days from the last day of preoperative or postoperative adjuvant chemotherapy are eligible for enrollment. 3.
Patients who are judged to be eligible for combination therapy with SOX and nivolumab by the physician in charge of the patient. 4.
4. the S-1 dose obtained from the BBT formula nomogram (page X) is increased from the starting dose described in the package insert.
5. the patient is at least 18 years of age at the time consent is obtained.
6. ECOG-Performance Status is 0,1
7. Capable of oral intake
8. Have at least one evaluable lesion on contrast-enhanced CT (chest, abdomen, pelvis: slice thickness less than 7 mm) within 28 days prior to registration.
9. Clinical laboratory tests performed within 14 days prior to enrollment meet the following criteria:
Neutrophil count over 1,500 /mm3
Platelet count over 10x104 /mm3
Hemoglobin over 8.0 g/dL
AST (GOT) under 100 U/L (under 200 U/L in case of liver metastasis)
ALT (GPT) under 100 U/L (under 200 U/L in case of liver metastasis)
Total bilirubin under 1.5 mg/dL
Creatinine under 1.5 mg/dL
10. Patients with agree to contraception.
11. Patient has given written consent to participate in the study.

Exclude criteria

1) Her2-positive gastric cancer (IHC: 3plus or IHC: 2plus with positive ISH)
2) Receiving enteral or intravenous nutritional support or requiring continuous infusion therapy
3) Patient has pericardial, pleural, or ascites fluid requiring drainage. However, if the fluid can be controlled by oral medication alone, it is acceptable.
4) Grade 2 or higher peripheral neuropathy
5) Brain or meningeal metastases. 5) Patients with brain or meningeal metastases, but brain imaging is not required for asymptomatic patients who do not require treatment.
6) Have multiple cancers (except completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, superficial bladder cancer, and other cancers that have not recurred for at least 5 years)
7) Received any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4, or other T-cell regulating antibody or pharmacologic therapy
8) Current or past severe hypersensitivity to other antibody drugs
9) Has a concomitant autoimmune disease or a history of autoimmune disease.
Patients with type 1 diabetes mellitus, hypothyroidism manageable with hormone replacement, and dermatological diseases not requiring systemic treatment (vitiligo, psoriasis, alopecia, etc.) may be enrolled.
10) Patients with complications or history of interstitial lung disease or pulmonary fibrosis: diagnosis must be based on CT findings
11) Patients with concomitant diverticulitis or symptomatic gastrointestinal ulcerative disease
12) Using warfarin, phenytoin, or flucytosine at the time of enrollment
13) Received or required systemic corticosteroids (except for temporary use for testing, prevention of allergic reactions, or reduction of edema due to radiation therapy) or immunosuppressive drugs within 28 days prior to enrollment
14) Have transient ischemic attack, cerebrovascular disease, thrombosis, or thromboembolism (pulmonary arterial embolism, deep vein thrombosis) within 180 days prior to enrollment.
15) History of any of the following cardiac diseases Myocardial infarction within 180 days prior to enrollment Uncontrolled angina pectoris within 180 days prior to study enrollment New York Heart Association (NYHA) Class3 or 4 congestive heart failure
16) Uncontrolled diabetes mellitus
17) Systemic infection requiring treatment
18) Underwent surgery (any surgery involving general anesthesia) within 28 days prior to enrollment
19) Had radiotherapy for gastric cancer within 28 days prior to enrollment or radiotherapy for bone metastases within 14 days prior to enrollment
20) Received radiopharmaceuticals within 56 days prior to enrollment (except for use of radiopharmaceuticals for laboratory or diagnostic purposes)
21) Received other unapproved drugs within 28 days (90 days for antibody drugs) prior to study enrollment
22) Positive for human immunodeficiency virus-1 (HIV-1), human immunodeficiency virus-2 (HIV-2), human T lymphotropic virus-1 (HTLV-1), hepatitis B surface protein (HBs) antigen, or hepatitis C virus (HCV) antibody
23) HBs antigen negative but HBs or HBc antibody positive with detectable hepatitis B virus deoxyribonucleic acid (HBV-DNA)
24) Pregnant, lactating, or possibly pregnant
25) Unable to give consent for specific reasons, such as concomitant dementia
26) Has received a live/weakly toxic vaccine within 28 days prior to study enrollment
27) Other individuals deemed inappropriate to participate in this study by the Principal Investigator(s)

Related Information

• Primary Sponsor: Suzuki Nobumi