Randomized Controlled Study of Postoperative Adjuvant Therapy for Gastric Cancer Using TS-1 or TS-1+PSK

Study Overview
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Brief Summary
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A randomized controlled study is conducted on patients with resected gastric cancer assigned to postoperative adjuvant therapy of TS-1 alone or PSK combined with TS-1, with the objective to examine or validate the outcome, QOL and prognostic factors (host and tumor factors), and explore the factors enhancing the antitumor effect of TS-1.

Detailed Description
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The 5-year survival after gastric cancer surgery remains poor as the cancer advances to stages II, IIIA, IIIB and IV. Tegafur-gimeracil-oteracil potassium (TS-1) is used as the first line treatment for advanced and recurrent gastric cancer. But TS-1 is accompanied by an adverse drug reaction of bone marrow suppression that is not readily seen in conventional oral fluoropyrimidines. Among randomized controlled trials on postoperative adjuvant chemotherapy for gastric cancer, the beneficial results of survival rates using Krestin (PSK) in combination with chemotherapy have been reported. With the objective to enhance the antitumor effect of TS-1 and to improve the QOL of patients, we have planned to validate the clinical significance of combined PSK and TS-1 therapy as postoperative adjuvant therapy for gastric cancer, using in principle the TS-1 regimen of 2-week dosing 1-week off for 6 months followed by 2-week dosing 2-week off for 6 months.

Official Title
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Randomized Multicenter Controlled Phase III Study of Postoperative Adjuvant Therapy for Stage II/IIIA Gastric Cancer Using TS-1 Alone or TS-1+PSK Combined Therapy

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Tegafur-gimeracil-oteracil potassium (TS-1)
* Drug: Krestin (PSK)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with microscopic stage II or IIIA resectable gastric cancer Patients who have not received preoperative cancer therapy (radiotherapy, chemotherapy or immunotherapy) Patients with serum immunosuppressive acidic protein (IAP) measured within 2 weeks before surgery Patients with no metachronous or synchronous multiple cancer Patients without severe impairment of renal, hepatic and bone marrow functions Patients who are judged to be capable of tolerating surgery Patients with preoperative performance status 0 to 2 Patients with no serious concurrent complications (such as bone marrow suppression, diarrhea and infection) Patients who are judged to be capable of tolerating this treatment, and who have given written informed consent to participate in this study Exclusion Criteria: Patients with fresh hemorrhage from the gastrointestinal tract Patients with retention of body fluid necessitating treatment Patients with infection, intestinal palsy or intestinal occlusion Patients who are pregnant or hope to become pregnant during the study period Patients with diabetes treated by continuous use of insulin or showing poor glycemic control Patients with a history of ischemic heart disease Patients with concurrent psychiatric disease or psychotic symptoms, and judged to have difficulties participating in the study Patients receiving continuous administration of steroids Patients who have experienced serious drug allergy in the past Others, patients judged by the investigator or subinvestigator to be inappropriate as subject

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>TS-1 Group: The group treated with TS-1 mono-therapy | Drug: Tegafur-gimeracil-oteracil potassium (TS-1)<br>* From 4-8 weeks after surgery to 27-31 weeks after surgery, 80 mg/m2, PO from day 1 to day 14 of each 21 day cycle. Number of Cycles: 8 From 28-32 weeks after surgery to 53-57 weeks after surgery, 80 mg/m2, PO from day 1 to day 14 of each 28 day cycle. Number of Cycles: 7<br>* Other names: TS-1;|
| Experimental: 2<br>TS-1+PSK Group: The group treated with combination therapy using TS-1 and PSK | Drug: Tegafur-gimeracil-oteracil potassium (TS-1)<br>* From 4-8 weeks after surgery to 27-31 weeks after surgery, 80 mg/m2, PO from day 1 to day 14 of each 21 day cycle. Number of Cycles: 8 From 28-32 weeks after surgery to 53-57 weeks after surgery, 80 mg/m2, PO from day 1 to day 14 of each 28 day cycle. Number of Cycles: 7<br>* Other names: TS-1;Drug: Krestin (PSK)<br>* From 4-8 weeks after surgery to 53-57 weeks after surgery, 3 g/day, PO every day<br>* Other names: PSK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of recurrence (calculation of 3-year disease-free survival and overall survival rates) |  | Five years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relations of survival rate with compliance, postoperative complication, QOL, adverse events, recurrence status, and expression of immune or tumor markers |  | Five years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, TS-1, PSK, Disease-free survival, Overall survival