A Phase I Study of S-1 in Combination With Radiotherapy in Locally Advanced or Recurrent Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine maximum tolerated dose (MTD), dose limiting toxicities (DLT) and recommend a proper dose for our phase II study of S-1 when combined with radiation therapy for locally advanced or recurrent gastric cancer.

Detailed Description
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This is a Phase I trial of S-1 given in treatment days with an oral dose from 30mg/m2/d to 80mg/m2/d, concurrently with radiation in patients with locally advanced or locally recurrent gastric cancer. Patients will be treated with external beam radiation therapy in a standard manner. S-1 will be administered for 6 dose levels,30/40/50/60/70/80mg/m2/d. Patients will be assessed for acute toxicities according to Common Toxicity Criteria for Adverse Effects (CTCAE)3.0.

Official Title
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A Phase I Study of S-1 in Combination With Radiotherapy in Locally Advanced or Recurrent Gastric Cancer

Conditions
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Gastrointestinal Neoplasms, Gastric Cancer

Intervention / Treatment
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* Drug: S-1
* Drug: S-1
* Drug: S-1
* Drug: S-1
* Drug: S-1
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven locally advanced gastric adenocarcinoma in patients undergoing R0, R1, R2 resection, or with unresectable or locoregional recurrent disease Any prior chemotherapy is allowed in this protocol. No distant metastasis in liver,lung,,bone,central nervous system(CNS),no peritoneal transplantation No prior abdominal or pelvic radiotherapy. Karnofsky performance status(KPS)≥ 70,predictive life span no less than 6 months Patients must have normal organ and marrow function as defined below: Leukocytes greater than or equal to 3,000 G/L Platelets: greater than or equal to 100,000/mm3 Hemoglobin:greater than or equal to 10g/L Total bilirubin: within normal institutional limits AST/ALT: less than or equal to 1.5 times the upper limit Creatinine within normal upper limits Informed consent Without any serious complications,such as hypertension,coronary artery disease,psychiatric history. Exclusion Criteria: Patients with other cancer history except cervical carcinoma in situ and non-malignant melanoma skin cancer With any distant metastasis in liver,lung,,bone,CNS,or peritoneal transplantation History of allergic reactions attributed to similar chemical or biologic complex to S-1 Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness History of myocardial infarction within the past 6 months or history of ventricular arrhythmia History of prior radiation to the abdomen Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-1,peroral BID,capsule<br> | Drug: S-1<br>* S-1,30mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.<br>* Other names: an oral fluorinated pyrimidine combination;Drug: S-1<br>* S-1,40mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.<br>* Other names: an oral fluorinated pyrimidine combination;Drug: S-1<br>* S-1,50mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner<br>* Other names: an oral fluorinated pyrimidine combination;Drug: S-1<br>* S-1,60mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.<br>* Other names: an oral fluorinated pyrimidine combination;Drug: S-1<br>* S-1,70mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.<br>* Other names: an oral fluorinated pyrimidine combination;Drug: S-1<br>* S-1,80mg/m2/d,peroral BID,in treatment days concurrently with radiation therapy in a standard manner.<br>* Other names: an oral fluorinated pyrimidine combination;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define dose limited toxicities(DLT) of S-1, peroral BID, in treatment days concurrently with radiation therapy (RT) in locally advanced or recurrent gastric cancer. | Dose limited toxicities defined as below: leucopenia ≥4 neutropenia ≥ 4, anemia ≥ 3, thrombocytopenia ≥ 3, alanine aminotransferase/aspartate aminotransferase (AST) ≥ 3, alkaline phosphatase (ALT) ≥ 3, total bilirubin ≥ 3,blood urea nitrogen (BUN)/Cr ≥ 2,non-granular cell decreased fever ≥ 2, nausea/vomiting ≥ 2, fatigue ≥ 3, weight loss ≥ 3, diarrhea ≥ 3, abdominal pain ≥ 3, dysphagia ≥ 3, hand-foot syndrome ≥ 2, neurotoxicity ≥ 2. | up to 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define maximum tolerated dose(MTD) of S-1, peroral BID, in treatment days concurrently with radiation therapy | If 1 of 3 patients treated within a S-1 dose level experiences DLTs, 3 more patients will be treated at the same level. If a second patient experiences DLTs, then escalation will be stopped and the MTD is defined as the level below DLT dose level. | up to 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined Modality, Gastric Cancer, Radiation Therapy, S-1