A Safety and Efficacy Study in Patients With Gastric Cancer

NCT ID: NCT00400179

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1053 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2008-04-30

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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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).

Group Type: ACTIVE_COMPARATOR

S-1/Cisplatin

Intervention Type: DRUG

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.

B

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.

Group Type: ACTIVE_COMPARATOR

5-FU/cisplatin

Intervention Type: DRUG

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.

Interventions

S-1/Cisplatin

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.

Intervention Type: DRUG

5-FU/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 Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabio Benedetti, MD

Role: STUDY_DIRECTOR

Taiho Oncology, Inc.

Locations

Clearview Cancer Center

Huntsville, Alabama, United States

Saint Joseph Medical Center

Burbank, California, United States

Dr. Ronald Yanagihara

Gilroy, California, United States

Norris Cancer Center

Los Angeles, California, United States

Comprehensive Cancer Center

Palm Springs, California, United States

Saint Francis Memorial Hospital

San Francisco, California, United States

Premiere Oncology

Santa Monica, 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

Straub Clinic and Hospital

Honolulu, Hawaii, United States

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Oncology and Hematology

Metairie, Louisiana, United States

St. Lukes Cancer Care Center

Duluth, Minnesota, United States

Neuroscience Center

St Louis, Missouri, United States

St. Louis University Cancer Center

St Louis, Missouri, United States

Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

AHS Lovelace Medical Group,LLC

Albuquerque, New Mexico, United States

New Mexico Cancer Center Associates

Albuquerque, New Mexico, United States

University of New Mexico

Albuquerque, New Mexico, United States

Hoo Chun, MD

Hawthorne, New York, United States

Hematology/Oncology Associates of Rockland

New City, New York, United States

New Bern Cancer Care

New Bern, North Carolina, United States

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Charleston Cancer Center

Charleston, South Carolina, United States

Associates in Oncology and Hematology

Chattanooga, Tennessee, United States

Lexington Oncology Associates

Chattanooga, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

CHUM Hopital Saint-Luc

Montreal, Quebec, Canada

Countries

United States; Canada

References

Bodoky G, Scheulen ME, Rivera F, Jassem J, Carrato A, Moiseyenko V, Vynnychenko I, Prausova J, Van Laethem JL, Cascinu S, Ajani JA. Clinical Benefit and Health-Related Quality of Life Assessment in Patients Treated with Cisplatin/S-1 Versus Cisplatin/5-FU: Secondary End Point Results From the First-Line Advanced Gastric Cancer Study (FLAGS). J Gastrointest Cancer. 2015 Jun;46(2):109-17. doi: 10.1007/s12029-014-9680-1.

Reference Type: DERIVED

PMID: 25707610 (View on PubMed)

Ajani JA, Buyse M, Lichinitser M, Gorbunova V, Bodoky G, Douillard JY, Cascinu S, Heinemann V, Zaucha R, Carrato A, Ferry D, Moiseyenko V. Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study. Eur J Cancer. 2013 Nov;49(17):3616-24. doi: 10.1016/j.ejca.2013.07.003. Epub 2013 Jul 27.

Reference Type: DERIVED

PMID: 23899532 (View on PubMed)

Other Identifiers

TPU S-1301

Identifier Type: -

Identifier Source: org_study_id

NCT00128609

Identifier Type: -

Identifier Source: nct_alias