Clinical trial NCT00400179: A Safety and Efficacy Study in Patients With Gastric Cancer
Official title: An Open-Label Multicenter, Randomized, Phase 3 Study of S-1 in Combination With Cisplatin Against 5-Fu in Combination W/ Cisplatin in Patients W/ Advanced Gastric Cancer Previously Untreated W/ Chemotherapy for Advanced Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Keywords: Gastric Cancer
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2006-11-16
Enrollment: 1053
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Median Survival
timeFrame: The cutoff date for survival analysis was 07 March 2008 (12 months after last patient randomized).
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Data cutoff was 07 March 2008 (12 months after last patient randomized).
measure: Duration of Response (DR)
timeFrame: Data cutoff was 07 March 2008 (12 months after last patient was randomized).
measure: Progression-free Survival (PFS)
timeFrame: 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.
measure: Time to Treatment Failure (TTF)
timeFrame: 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.
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Center
state: Alabama
city: Burbank
country: United States
facility: Saint Joseph Medical Center
state: California
city: Gilroy
country: United States
facility: Dr. Ronald Yanagihara
state: California
city: Los Angeles
country: United States
facility: Norris Cancer Center
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Saint Francis Memorial Hospital
state: California
city: Santa Monica
country: United States
facility: Premiere Oncology
state: California
city: Lakewood
country: United States
facility: Western Hematology/Oncology
state: Colorado
city: Fort Lauderdale
country: United States
facility: Broward Oncology Associates
state: Florida
city: Tampa
country: United States
facility: Alexandar Rosemurgy
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Metairie
country: United States
facility: Oncology and Hematology
state: Louisiana
city: Duluth
country: United States
facility: St. Lukes Cancer Care Center
state: Minnesota
city: Saint Louis
country: United States
facility: Neuroscience Center
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: Southern Nevada Cancer Research Foundation
state: Nevada
city: Albuquerque
country: United States
facility: AHS Lovelace Medical Group,LLC
state: New Mexico
city: Albuquerque
country: United States
facility: New Mexico Cancer Center Associates
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Hawthorne
country: United States
facility: Hoo Chun, MD
state: New York
city: New City
country: United States
facility: Hematology/Oncology Associates of Rockland
state: New York
city: New Bern
country: United States
facility: New Bern Cancer Care
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: Associates in Oncology and Hematology
state: Tennessee
city: Chattanooga
country: United States
facility: Lexington Oncology Associates
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Montreal
country: Canada
facility: CHUM Hopital Saint-Luc
state: Quebec
Study officials:
affiliation: Taiho Oncology, Inc.
name: Fabio Benedetti, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.