A Safety and Efficacy Study in Patients With Gastric Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Gastric Cancer	Drug: S-1/Cisplatin Drug: 5-FU/cisplatin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Stomach Cancer

Drug Information available for: Fluorouracil Cisplatin

U.S. FDA Resources

Further study details as provided by Taiho Pharma USA, Inc.:

Primary Outcome Measures:

Median Survival [ Time Frame: The cutoff date for survival analysis was 07 March 2008 (12 months after last patient randomized). ] [ Designated as safety issue: No ]
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:

Overall Response Rate (ORR) [ Time Frame: Data cutoff was 07 March 2008 (12 months after last patient randomized). ] [ Designated as safety issue: No ]
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.
Duration of Response (DR) [ Time Frame: Data cutoff was 07 March 2008 (12 months after last patient was randomized). ] [ Designated as safety issue: No ]
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.
Progression-free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
The time from randomization to date of first documented PD or date of death, whichever occurred first.
Time to Treatment Failure (TTF) [ Time Frame: 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. ] [ Designated as safety issue: No ]
The time from randomization to date of permanent discontinuation of S-1 or 5-FU, first documented PD, or death, whichever occurred first.

Enrollment:	1053
Study Start Date:	May 2005
Study Completion Date:	April 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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).	Drug: 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.
Active Comparator: 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.	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.

Arms

Assigned Interventions

Active Comparator: 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).

Drug: 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.

Active Comparator: 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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00400179

Show 33 Study Locations

Sponsors and Collaborators

Taiho Pharma USA, Inc.

Quintiles

Investigators

Study Director:

Fabio Benedetti, MD

Taiho Pharma USA, Inc.

More Information

No publications provided

Responsible Party:	Taiho Pharma USA, Inc.
ClinicalTrials.gov Identifier:	NCT00400179 History of Changes
Obsolete Identifiers:	NCT00128609
Other Study ID Numbers:	TPU S-1301
Study First Received:	June 30, 2005
Results First Received:	January 6, 2012
Last Updated:	March 28, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Taiho Pharma USA, Inc.:

Gastric Cancer

Additional relevant MeSH terms:

Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Cisplatin
Fluorouracil

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 21, 2013