Trial of 3-weekly Versus 5-weekly Schedule of S-1 Plus Cisplatin in Gastric Cancer (SOS)

This study has been completed.
Sponsor:
Collaborators:
Samsung Medical Center
Kyungpook National University
Seoul Veterans Hospital
National Cancer Center, Korea
Ulsan University Hospital
Inje University
Chonbuk National University Hospital
Gachon University Gil Medical Center
Korea Cancer Center Hospital
Yeungnam University College of Medicine
Hallym University Medical Center
Chonnam National University Hospital
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00915382
First received: June 5, 2009
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

The urgent need for a new effective therapy with better safety profile for the metastatic gastric cancer patients and promising results observed so far in the studies with S-1 plus cisplatin combination in advanced gastric cancer (AGC) strongly warrants the comparison of a 3-weekly schedule to a 5-weekly schedule of S-1 plus cisplatin as a standard regimen in the first-line treatment for AGC patients.

The objectives of this study are to compare a 3-weekly schedule to a 5-weekly schedule of S-1 plus Cisplatin combination in terms of efficacy, quality of life and safety in patients with previously untreated advanced or recurrent unresectable gastric cancer. Primary endpoint is progression-free survival. This is an open label, randomized, multi-center, non-inferiority/superiority (of 3-weekly regimen over 3-weekly regimen) hybrid study.


Condition Intervention Phase
Advanced Gastric Cancer
Drug: S-1 and cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial of 3-weekly vs. 5-weekly Schedule of S-1 Plus Cisplatin Combination Chemotherapy for First Line Treatment of Advanced Gastric Cancer.

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • progression-free survival [ Time Frame: accrual of patients for 36 months, followup of the last patient for 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: accrual of patients for 36 months, followup of the last patient for 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 625
Study Start Date: January 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 3 weekly regimen of S-1 and cisplatin Drug: S-1 and cisplatin

S-1: 80 mg/m2/day po on Days 1-14

cisplatin: 60 mg/m2 iv on Day 1

Other Name: TS-1 and cisplatin
Active Comparator: 5 weekly regimen of S-1 and cisplatin Drug: S-1 and cisplatin

S-1: 80 mg/day with BSA less than 1.25 m2, 100 mg/day with BSA more than 1.25 m2 and less than 1.5 m2, 120 mg/day with BSA more than 1.5 m2 on Days 1-21 and

cisplatin: 60 mg/m2 iv on Day 1 or 8

Other Name: TS-1 and cisplatin

Detailed Description:

The primary endpoint of this study is Progression Free Survival (PFS). It is defined as the time from the date of randomization to the time of disease progression as assessed by the investigators, or death due to any cause. The primary goal of this study is to compare two different schedules of S-1 plus cisplatin combination treatments (3-weekly regimen vs. 5-weekly regimen) for advanced gastric cancer with respect to the PFS based on the hybrid design where we can test superiority and non-inferiority in the same trial (Reference: Journal of Clinical Oncology 25: 5019-5023, 2007, Boris Freidlin, et el). First, the non-inferiority hypothesis will be tested based on the non-inferiority margin 1.15. If the inferiority cannot be rejected(meaning non-inferiority is proven) then the superiority will be tested. If the superiority test is positive, then superiority is concluded; otherwise non-inferiority without superiority will be concluded.

The sample size was calculated from the following consideration:

For non-inferiority test: non-inferiority margin 1.15, 10 percent reduction of hazard ratio, power 80 percent, alpha 0.025, accrual period 36 months, follow-up period 12 months, and the expected median PFS of 6 months for 5 weekly regimen were assumed. Based on the above considerations, total of 560 patients will be need. With 10 percent follow-up loss, we need 622 patients.

For superiority test: the median PFS for 5-weekly regimen is expected to be 6 months and 7.5 months for 3-weekly regimen. With sample size of 560 patients calculated above, for detecting 1.5 months difference in the median PFS between the two groups , we will have 81 percent of power, one-sided 5 percent type I error. Using the log rank test assuming exponential underlying distribution, accrual period of 36 months, minimum of 12 months follow-up after the last enrolment, 516 events will be needed to show the superiority of 3 week cycle.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented metastatic or recurrent gastric adenocarcinoma including adenocarcinoma of the gastro-esophageal junction
  • Age 18 to 74 years old
  • Performance status (ECOG scale) 0-2
  • No significant problems for oral intake and drug administration
  • At least one measurable or evaluable disease defined by RECIST
  • Adequate bone marrow function (ANC ≥ 1,500/uL, Platelet ≥ 100,000/ uL, Hb ≥ 9.0 g/dl)
  • Adequate renal function: serum creatinine ≤ UNL (if serum creatinine > UNL, creatinine clearance should be ≥ 60 mL/min)
  • Adequate hepatic function (Total bilirubin < 2 x UNL and AST/ALT levels < 3 x UNL without liver metastasis,total bilirubin < 3x ULN and AST/ALT levels < 5 x UNL with liver metastasis)
  • Prior systemic therapy (for instance, cytotoxic chemotherapy or active/passive immunotherapy) is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrolment into the study) and cisplatin was not used before
  • Patients should sign a written informed consent before study entry

Exclusion Criteria:

  • Tumor type other than adenocarcinoma
  • Previously exposed to any fluropymidine within 6 months before the study
  • Previously exposed to Platinum therapy regardless of its period and/or duration
  • Microscopic residual disease only after noncurative gastrectomy with R1 resection (resection margin positive)
  • Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence)
  • Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before randomization
  • Presence of CNS metastasis
  • Major surgery within 4 weeks before initiation of study treatment or lack of complete recovery from the effects of major surgery (patient received curative operation or RFA for metastatic disease)
  • Serious illness or medical conditions:

    • Congestive heart failure (NYHA class III or IV)
    • Unstable angina or myocardial infarction within the past 12 months
    • Significant arrhythmias requiring medication and conduction abnormality such as over 2nd degree AV block
    • Uncontrolled hypertension
    • Hepatic cirrhosis (≥ Child class B)
    • Interstitial pneumonia
    • Pulmonary adenomatosis
    • Psychiatric disorder that may interfere with protocol compliance
    • Unstable diabetes mellitus
    • Uncontrolled ascites or pleural effusion
    • Active infection
  • Receiving a concomitant treatment interacting with S-1 or cisplatin:

    • Flucytosine (a fluorinated pyrimidine antifungal agent)
    • Antivirals such as sorivudine, ramivudine, brivudine or other chemically related agents, warfarin, phenprocoumon, phenytoin, allopurinol
  • Pregnant or lactating woman
  • Women of child bearing potential not using a contraceptive method
  • Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential
  • Any patients judged by the investigator to be unfit to participate in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00915382

Locations
Korea, Republic of
Department of Oncology, Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Samsung Medical Center
Kyungpook National University
Seoul Veterans Hospital
National Cancer Center, Korea
Ulsan University Hospital
Inje University
Chonbuk National University Hospital
Gachon University Gil Medical Center
Korea Cancer Center Hospital
Yeungnam University College of Medicine
Hallym University Medical Center
Chonnam National University Hospital
Investigators
Principal Investigator: Yoon-Koo Kang, MD, PhD Asan Medical Center, Seoul, Korea
Principal Investigator: Won Ki Kang, M.D.PhD. Samsung Medical Center, Seoul, Korea
Principal Investigator: Jong Kwang Kim, M.D.PhD Kyungpook National University Hospital, Korea
Principal Investigator: Young Iee Park, M.D.PhD National Cancer Center, Korea
Principal Investigator: Jin Ho Baek, M.D.PhD. Ulsan University Hospital, Korea
Principal Investigator: Chang Hak Sohn, M.D.PhD. Inje University Pusan Paik Hospital, Korea
Principal Investigator: Eun Ki Song, M.D.PhD. Chonbuk National University Hospital, Korea
Principal Investigator: Dong Bok Shin, M.D.PhD. Gachon University Gil Medical Center
Principal Investigator: Sung Hyun Yang, M.D.PhD. Korea Cancer Center Hospital
Principal Investigator: Kyung Hee Lee, M.D.PhD. Yeungnam University College of Medicine
Principal Investigator: Dae Young Zang, M.D.PhD Hallym University Medical Center
Principal Investigator: Ik-Joo Chung, M.D.PhD Chonnam National University Hospital
  More Information

No publications provided

Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00915382     History of Changes
Other Study ID Numbers: SOS
Study First Received: June 5, 2009
Last Updated: January 13, 2014
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 26, 2014