A Safety and Efficacy Study in Patients With Gastric Cancer

Phase 3

Completed

Conditions: Gastric Cancer

Interventions: Drug: S-1/Cisplatin
Drug: 5-FU/cisplatin

Registration Number: NCT00400179

Lead Sponsor: Taiho Oncology, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1053

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	S-1/Cisplatin	In Arm A, S-1 25 mg/m² was administered orally BID from Day 1 through Day 21 followed by a recovery period from Days 22 through Day 28. On Day 1, the morning dose of S-1 was administered before cisplatin 75 mg/m2 administration as a 1- to 3-hour IV infusion. This regimen was repeated every 4 weeks. S-1 was administered one hour before or one hour after a meal with a glass of water (approximately 100 mL).
B	5-FU/cisplatin	In Arm B, 5-FU 1000 mg/m2/24 hours was administered by continuous intravenous infusion (CIV) over 120 hours (on Days 1 through 5). This regimen was repeated every 4 weeks. 5-FU CIV followed cisplatin infusion on Day 1. All 5-FU used in this study was commercially available product.

Primary Outcome Measures

Name	Time	Method
Median Survival	The cutoff date for survival analysis was 07 March 2008 (12 months after last patient randomized).	Survival was defined as the time from the date of randomization to the time of death (from any cause) for each patient.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DR)	Data cutoff was 07 March 2008 (12 months after last patient was randomized).	Duration of response was defined as the time from date of first confirmed response (CR or PR) to date of first progressive disease (PD) or death. Per the RECIST criteria, definitions were as follows: CR was the disappearance of all target lesions for at least 4 weeks, PR was at least a 30% decrease in the sum of the longest diameter of target lesions, and PD was at least a 20% increase in the sum of the longest diameter of target lesions.
Overall Response Rate (ORR)	Data cutoff was 07 March 2008 (12 months after last patient randomized).	The proportion of patients with objective evidence of complete response (CR) or partial response (PR) based on tumor response assessments. Per the Response Evaluation Criteria in Solid tumors (RECIST), CR was defined as the disappearance of all target lesions for at least 4 weeks, and PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions.
Progression-free Survival (PFS)	From date of randomization until date of first documented PD, date of death, or until data cutoff on 07 March 2008 (12 months after last patient randomized), whichever came first.	The time from randomization to date of first documented PD or date of death, whichever occurred first.
Time to Treatment Failure (TTF)	From date of randomization until date of permanent discontinuation of S-1 or 5-FU, first documented PD, death, or data cutoff on 07 March 2008 (12 months after last patient randomized), whichever came first.	The time from randomization to date of permanent discontinuation of S-1 or 5-FU, first documented PD, or death, whichever occurred first.

Trial Locations

Locations (33): Saint Joseph Medical Center
🇺🇸
Burbank, California, United States
Abramson Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Southern Nevada Cancer Research Foundation
🇺🇸
Las Vegas, Nevada, United States
Straub Clinic and Hospital
🇺🇸
Honolulu, Hawaii, United States
Saint Francis Memorial Hospital
🇺🇸
San Francisco, California, United States
Dr. Ronald Yanagihara
🇺🇸
Gilroy, California, United States
Clearview Cancer Center
🇺🇸
Huntsville, Alabama, United States
Norris Cancer Center
🇺🇸
Los Angeles, California, United States
Comprehensive Cancer Center
🇺🇸
Palm Springs, California, United States
Western Hematology/Oncology
🇺🇸
Lakewood, Colorado, United States
Broward Oncology Associates
🇺🇸
Fort Lauderdale, Florida, United States
Alexandar Rosemurgy
🇺🇸
Tampa, Florida, United States
Palm Beach Cancer Institute
🇺🇸
West Palm Beach, Florida, United States
Robert H. Lurie Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
St. Lukes Cancer Care Center
🇺🇸
Duluth, Minnesota, United States
Oncology and Hematology
🇺🇸
Metairie, Louisiana, United States
Neuroscience Center
🇺🇸
Saint Louis, Missouri, United States
St. Louis University Cancer Center
🇺🇸
Saint Louis, Missouri, United States
New Mexico Cancer Center Associates
🇺🇸
Albuquerque, New Mexico, United States
AHS Lovelace Medical Group,LLC
🇺🇸
Albuquerque, New Mexico, United States
University of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Hoo Chun, MD
🇺🇸
Hawthorne, New York, United States
New Bern Cancer Care
🇺🇸
New Bern, North Carolina, United States
Hematology/Oncology Associates of Rockland
🇺🇸
New City, New York, United States
Premiere Oncology
🇺🇸
Santa Monica, California, United States
Lexington Oncology Associates
🇺🇸
Chattanooga, Tennessee, United States
Associates in Oncology and Hematology
🇺🇸
Chattanooga, Tennessee, United States
CHUM Hopital Saint-Luc
🇨🇦
Montreal, Quebec, Canada
Charleston Cancer Center
🇺🇸
Charleston, South Carolina, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸
Madison, Wisconsin, United States
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States