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S-1 and Cisplatin (3 Weekly) Versus S-1 and Oxaliplatin Combination Chemotherapy for Advanced Gastric Cancer

Phase 3
Completed
Conditions
Gastric Cancer
Interventions
Registration Number
NCT01671449
Lead Sponsor
Min-Hee Ryu
Brief Summary

A multicenter, randomized, open-label, phase III trial of S-1 plus cisplatin (3 weekly) versus S-1 plus oxaliplatin chemotherapy for the first-line treatment of advanced gastric cancer

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
338
Inclusion Criteria
  1. Written informed consent before the enrollment

  2. Age ≥18 years old

  3. Histologically/cytologically confirmed recurrent or metastatic gastric or esophagogastric junctional adenocarcinoma

  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

  5. Patients able to swallow food and drugs

  6. At least one measurable or evaluable lesion according to RECIST criteria version 1.1

  7. Adequate bone, hepatic, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to first administration of study drugs

    • Absolute neutrophil count (ANC) ≥ 1,500/ uL, platelet ≥ 100,000/ uL, haemoglobin (Hb) ≥ 9.0 g/dl,
    • Serum creatinine ≤ 1.5 mg/dL (If serum creatinine is greater than 1.5 mg/dL, creatinine clearance [Ccr] should be 60 mL/min or greater. Ccr is calculated by Cockcroft-Gault formula or 24hr urine collection)
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST/ALT levels ≤ 3.0 x ULN (AST/ALT levels ≤ 5.0 x ULN for patients with liver involvement of their cancer)
  8. In patients who received adjuvant or neoadjuvant chemotherapy, completion of systemic chemotherapy 6 months before the study enrollment, and no previous administration of platinum derivatives

  9. Estimated life expectancy of more than 3 months

Exclusion Criteria
  1. Other histologic types than adenocarcinoma

  2. Recurrence within 24 weeks following completion of adjuvant chemotherapy

  3. R1 gastrectomy (i.e., microscopic residual disease)

  4. History of another malignancy within the last five years from the day of written informed consent except cured basal cell carcinoma of skin and cured carcinoma in situ of uterine cervix

  5. Radiotherapy within 4 weeks after randomization

  6. History of significant neurologic or psychiatric disorders, and presence or history of CNS metastasis

  7. Major surgery within 4 weeks before study entry, or insufficient recovery from major surgery (except the patients who received only open and closure or biopsy)

  8. Other serious illness or medical conditions as follows;

    • Any following conditions occurred within 6 months before study entry: myocardial infarction, severe/unstable angina, bypass surgery for coronary artery/peripheral artery, congestive heart failure (NYHA class III or IV), cerebral infarction or transient ischemic attack
    • Conduction abnormality such as 2nd degree or greater AV block or severe arrhythmia that requires medical treatments (right bundle branch block (RBBB) is eligible, but left bundle branch block (LBBB) is not.)
    • Uncontrolled hypertension
    • Liver cirrhosis (Child Pugh Class B or greater)
    • Interstitial pneumonia, pulmonary fibrosis
    • Active viral hepatitis B
    • Uncontrolled diabetes mellitus
    • Uncontrolled ascites or pleural effusion
    • Uncontrolled active infection or sepsis
  9. Administration of medications which may have potentially pharmacokinetic interaction with S-1, cisplatin, and oxaliplatin

    • Flucytosine, a fluorinated pyrimidine antifungal agent
    • Anti-viral agents, such as sorivudine, and brivudine, or chemical similar drugs
    • Warfarin (except, low dose warfarin for the purpose of prophylaxis), phenprocoumon
    • Phenytoin
    • Allopurinol
  10. Participation to other clinical trials or administration of other investigational drugs within 30 days before the randomisation

  11. Pregnant or lactating women

  12. Women or men of child bearing potential not employing adequate contraception during study treatments or until the 3 months after the end of study treatments

  13. Ineligible for the study at the discretion of investigators

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
S-1 plus CisplatinCisplatin* S-1: 40 mg/m2, twice daily, p.o., day 1-14 (see Table 6 for dose calculation of S-1 according to body surface area) : If S-1 is started on the evening of day 1, last dose of S-1 will be administered at the morning of day 15. * Cisplatin: 60 mg/ m2/day, i.v., day 1 * Every 3 weeks
S-1 plus CisplatinS-1* S-1: 40 mg/m2, twice daily, p.o., day 1-14 (see Table 6 for dose calculation of S-1 according to body surface area) : If S-1 is started on the evening of day 1, last dose of S-1 will be administered at the morning of day 15. * Cisplatin: 60 mg/ m2/day, i.v., day 1 * Every 3 weeks
S-1 plus OxaliplatinS-1* S-1: 40 mg/m2, twice daily, p.o., day 1-14 (see Table 6 for dose calculation of S-1 according to body surface area) : If S-1 is started on the evening of day 1, last dose of S-1 will be administered at the morning of day 15. * Oxaliplatin: 130 mg/ m2/day, i.v., day 1 * Every 3 weeks
S-1 plus OxaliplatinOxaliplatin* S-1: 40 mg/m2, twice daily, p.o., day 1-14 (see Table 6 for dose calculation of S-1 according to body surface area) : If S-1 is started on the evening of day 1, last dose of S-1 will be administered at the morning of day 15. * Oxaliplatin: 130 mg/ m2/day, i.v., day 1 * Every 3 weeks
Primary Outcome Measures
NameTimeMethod
Progression-free survivalFrom date of randomization to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

The primary endpoint of this study is progression-free survival. This is defined as the time from randomization to disease progression or death due to any cause.

Secondary Outcome Measures
NameTimeMethod
Number of Adverse EventsEvery 3 weeks

Monitoring for safety and toxicity will be performed every cycle (3 weeks) of chemotherapy and whenever patients have problems.

Overall survivalFrom date of randomization to death from any cause, assessed up to 3 years

Overall survival is defined as the time from randomization to death due to any cause.

Response rateEvery 6 weeks

Response assessment will be performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 every 2 cycles (6 weeks) of treatment.

Quality of lifeEvery 6 weeks

Quality of life of patient will be evaluated using EUROQOL(EQ-5D). Evaluation of quality of life will be performed every 2 cycles (6 weeks) from baseline to the end of treatment.

Trial Locations

Locations (9)

Chonnam National University Hwasun Hospital

🇰🇷

Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea, Republic of

Dongnam Institute of Radiological and Medical Sciences

🇰🇷

Busan, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Bundang-gu, Seongnam-si, Gyeonggi-do, Korea, Republic of

National Cancer Center

🇰🇷

Ilsan, Gyeonggi-do, Korea, Republic of

Yeungnam University Medical Center

🇰🇷

Daegu, Korea, Republic of

Gangneung Asan Hospital

🇰🇷

Gangneung-si, Korea, Republic of

Seoul St. Mary's hospital of the Catholic University of Korea

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Chungbuk National University Hospital

🇰🇷

Cheongju-si, Chungcheongbuk-do, Korea, Republic of

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