A Phase 1, Open-Label, Non-Randomized, Dose-Finding, Safety and Tolerability Study of Orally Administered Teysuno (S-1) in Combination with Epirubicin and Oxaliplatin in Patients with Advanced Solid Tumors: Part 2 – Esophagogastric Cancer

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 12

Inclusion Criteria

1. Has given written informed consent.
2. Is =18 years of age.
3. Has advanced or metastatic esophagogastric adenocarcinoma.
4. No previous treatment for advanced or metastatic disease.
5. Is able to take medications orally.
6. Has ECOG performance status 0 or 1 on Cycle 1, Day 1.
7. Has a life expectancy of at least 3 months.
8. Left ventricular ejection fraction (LVEF) = the lower limit of normal (LLN) for the institution.
9. Serum troponin T and creatine phosphokinase (CPK)-MB values = upper limit of Normal (ULN) for the institution.
10. Has adequate organ function as defined by the following criteria:
a. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) =2.5 x ULN; if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) =5 x ULN.
b. Total serum bilirubin of =1.5 x ULN.
c. Absolute neutrophil count of =1,500/mm3 (ie, =1.5 x 109/L by International Units [IU])
(excluding measurements obtained within 7 days after administration of G-CSF).
d. Platelet count =100,000/mm3 (IU: =100 x 109/L) (excluding measurements obtained within 7 days after transfusion).
e. Hemoglobin value of =9.0 g/dL (excluding measurements obtained within 7 days after
transfusion).
f. Creatinine clearance =60 mL/min based on calculated creatinine clearance (Cockcroft-
Gault32 formula) or 24-hour urine collection.
11. Is willing and able to comply with scheduled visits, treatment plan, lab tests and other study procedures.

Exclusion Criteria

1. Has had treatment with any of the following within the specified time frame prior to study drug administration:
a. Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to study drug administration).
b. Radiotherapy within prior 4 weeks.
c. Previous chemotherapy.
i. Any investigational agent received either concurrently or within the last 30 days.
j. Current enrollment in another interventional clinical study.
2. Has a serious illness or medical condition(s) including, but not limited to, the following:
a. Known brain metastasis or leptomeningeal metastasis.
b. Known acute systemic infection.
c. Myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, pulmonary embolism, or deep vein thrombosis within the last 12 months.
d. Symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV e. Ongoing cardiac dysrhythmias (=Grade 2),
atrial fibrillation (any grade), or prolongation of QTc interval (>450 msec for males; >470 msec for females).
f. Hypertensive crisis or severe hypertension that is not controlled.
g. Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator.
h. =Grade 1 peripheral neuropathy.
i. Recent hemoptysis, coagulopathy and other bleeding disorders considered by the Investigator to be clinically significant.
j. Known nephrotic syndrome (proteinuria >2 g/24 hours).
k. Known clinically significant interstitial lung disease or pulmonary fibrosis.
l. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
m. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the
interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
3. Is receiving concomitant treatment with the following drugs that may interact with S-1:
a. Sorivudine, brivudine, uracil, eniluracil, cimetidine, folinate/folinic acid, and dipyridamole (may enhance S-1 activity).
b. Nitroimidazoles, including metronidazole and misonidazole (may enhance S-1 activity)
c. Methotrexate (may enhance S-1 activity)
d. Clozapine (may increase risk and severity of hematologic toxicity with S-1)
e. Allopurinol (may diminish S-1 activity).
f. Phenytoin (S-1 may enhance phenytoin activity).
g. Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 activity).
4. Is receiving concomitant treatment with the following drugs that may interaction with epirubicin:
a. Cimetidine (may increase the area under the plasma concentrationtime curve [AUC] of epirubicin).
b. Dexverapamil (may alter the pharmacokinetics of epirubicin).
c. Quinine (may accelerate the initial distribute on of epirubicin from blood into the tissues and may have an influence on the red blood cells partitioning of epirubicin).
d. Interferon alfa-2b (may cause a reduction in both the terminal elimination half-life and the total clearance of epirubicin).
5. Is a pregnant or lactating female.
6. Has known hypersensitivity to 5-FU, epirubicin, oxaliplatin or other platinum compounds.
7. Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients). Contraceptive measures must be taken b

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To investigate the safety and determine the maximum tolerated dose (MTD) of S-1 25 mg/m2, when combined with epirubicin 50 mg/m2 and oxaliplatin 130 <br>mg/m2 in patients with advanced or metastatic esophagogastric cancer as first line therapy.<br>Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 will be used.

Secondary Outcome Measures

Name	Time	Method
To document any antitumor activity observed with S-1 administered in this combination<br>treatment regimen.<br>Tumor assessments will be performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009). Computed tomography (CT) scans will be performed at the end of every 3 cycles.

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Updated 9/4/2023