A Safety and Efficacy Study in Patients With Gastric Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: S-1/Cisplatin; 5-FU/cisplatin
Intervention description: In Arm A, S-1 25 mg/m2 was taken orally two times daily for 21 days followed by a 7-day recovery period. The patient was instructed to have nothing by mouth (NPO 1 hour prior to and 1 hour after S-1 administration. S-1 was taken with approximately 8 ounces of water and prior to cisplatin infusion on Day 1.
Cisplatin 75 mg/m2 was administered as a 1- to 3-hour IV infusion after the morning dose of S-1 on Day 1 of each cycle. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment for cisplatin.; In Arm B, 5-FU 1000 mg/m2/24 hours was administered CIV on Days 1 through 5 following cisplatin 100 mg/m2 administered IV as a 1- to 3-hour infusion on Day 1. This regimen was repeated every 4 weeks with a maximum of 6 cycles of treatment for cisplatin.
Intervention MeSH terms: Cisplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1053.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric Cancer

Summary:

      This is an open-label, international, two-arm, parallel, randomized, Phase 3 study evaluating
      the efficacy and safety of S-1/cisplatin versus 5-FU/cisplatin in patients with advanced
      gastric cancer previously untreated with chemotherapy for advanced disease. Patients will be
      randomly assigned (1:1) to S-1/cisplatin (experimental arm) or 5-FU/cisplatin (control arm).
      Patients will be stratified by number of metastatic sites (one vs. more than one), locally
      advanced or metastatic disease, prior adjuvant therapy (yes or no), measurable or
      non-measurable disease, and center.
    

Eligibility criteria:

        Inclusion Criteria:

        A patient must meet all of the following inclusion criteria to be eligible for enrollment
        in this study:

          -  Has given written informed consent

          -  Has histologically confirmed, unresectable, locally advanced (Stage IV) or metastatic
             gastric cancer, including adenocarcinoma of the gastro-esophageal junction

          -  Has measurable or evaluable but non-measurable disease, defined as follows:

               -  Measurable Disease - Patients with measurable disease as defined by RECIST
                  criteria, i.e., the presence of at least one measurable lesion. A measurable
                  lesion is one that can be accurately measured in at least one dimension with the
                  longest diameter >_ 20 mm using conventional techniques or >_ 10 mm using spiral
                  Computed Tomography (CT)scan. Locally recurrent disease (other than primary) is
                  accepted if there is at least one measurable lesion (i.e. peritoneal mass, lymph
                  node, etc.)

               -  Evaluable but Non-measurable Disease - Patients with all lesions below the limits
                  defined above for measureable disease (i.e., longest diameter < 20 mm with
                  conventional techniques or < 10 mm with spiral CT) excluding those patients with
                  only a primary lesion and/or with only non-evaluable cancer such as bone
                  metastases, ascites, pleural or pericardia effusions, lymphangitic carcinomatosis
                  of the skin or lung, previously irradiated lesions not in progression, or
                  peritoneal carcinomatosis < 10 mm in diameter with conventional imaging
                  techniques.

          -  No prior palliative chemotherapy is permitted. Adjuvant and /or neo-adjuvant
             chemotherapy is permitted if more than 12 months have elapsed between the end of
             adjuvant or neo-adjuvant therapy and first recurrence. This does not qualify as 1st
             line therapy.

          -  Is able to take medications orally

          -  Is >_ 18 years of age

          -  Is at least 3 weeks from prior major surgery

          -  Is at least 4 weeks from prior radiotherapy

          -  Has a ECOG performance status 0 to 1

          -  Has adequate organ function as defined by the following criteria:

               -  AST (SGOT) and ALT (SGPT) <_ 2.5 x ULN; if liver function abnormalities are due
                  to underlying liver metastasis, AST (SGOT) and ALT (SGPT) <_ 5 x ULN

               -  Total serum bilirubin of <_ 1.5 x ULN

               -  Absolute granulocyte count of >_ 1,500/mm (i.e. >_ 1.5 x 10/L by International
                  Units (IU)

               -  Platelet count >_ 100,000/mm (IU: >_ 100 x 10/L

               -  Hemoglobin value of >_ 9.0 g/dL

               -  Calculated creatinine clearance >_ 60 mL/min (Cockcroft-Gault formula)

          -  Is willing and able to comply with scheduled visits, treatment plans, laboratory tests
             and other study procedures

        Exclusion Criteria:

        Exclude a patient from this study if he/she does not fulfill the inclusion criteria, or if
        any of the following conditions are observed:

          -  Has had a treatment with any of the following within the specified timeframe prior to
             study drug administration:

               -  Any prior palliative chemotherapy or any previous therapy for malignancy,
                  including any chemotherapy, immunotherapy, biologic or hormonal therapy, within
                  the past 5 years.

               -  Adjuvant or neo-adjuvant therapy within the past 12 months

               -  Concurrent treatment with any investigational anti-cancer agent

               -  Prior cisplatin as neo-adjuvant and /or adjuvant chemotherapy with cumulative
                  dose > 300 mg/m

               -  > 25% of marrow-bearing bone radiated

               -  Concurrent treatment with an investigational agent or within 30 days from
                  randomization

               -  Concurrent enrollment in another clinical study

          -  Has a serious illness or medical condition(s) including, but not limited to the
             following:

               -  Known brain or leptomeningeal metastases

               -  Uncontrolled ascites requiring drainage at least twice a week

               -  Other malignancies within the past 5 years, except adequately treated
                  carcinoma-in-situ of the cervix or non-melanoma skin cancer

               -  Myocardial infarction within the last 6 months, severe/unstable angina,
                  congestive heart failure New York Heart Association (NYHA) class III or IV

               -  Chronic nausea, vomiting or diarrhea

               -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
                  (AIDS-related illness

               -  Psychiatric disorder that may interfere with consent and/or protocol compliance

               -  Known neuropathy, Grade 2 or higher

               -  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 judgement of the Investigator would make the patient
                  inappropriate for entry into this study

          -  Is receiving concomitant treatment with drugs interacting with S-1. The following
             drugs are prohibited because there may be an interaction with S-1:

               -  Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1
                  activity)

               -  Allopurinol (may diminish S-1 activity

               -  Phenytoin (S-1 may enhance phenytoin activity)

               -  Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 activity)

          -  Is receiving concomitant treatment with drugs interacting with 5-FU:

               -  Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole(may enhance 5-FU
                  activity)

               -  Allopurinol (may diminish 5-FU activity)

               -  Phenytoin (5-FU may enhance phenytoin activity)

          -  Is receiving concomitant treatment with drugs interacting with cisplatin:

               -  Phenytoin (cisplatin may diminish phenytoin activity)

               -  Aminoglycosides (should be avoided within 8 days after cisplatin administration)

               -  Ethyol (may diminish cisplatin activity

          -  Is a pregnant or lactating female

          -  Has known hypersensitivity to 5-FU or cisplatin

          -  Patients with reproductive potential who refuse to use an adequate means of
             contraception (including male patients)