Chemotherapy, Surgery, and Radiation Therapy in Treating Patients With Gastric Cancer
- Conditions
- Gastric Cancer
- Interventions
- Procedure: surgeryRadiation: radiation therapy
- Registration Number
- NCT00003298
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells. E7296 was conducted to study neoadjuvant chemotherapy and postoperative chemoradiation therapy in patients diagnosed with high-risk gastric cancer using a new neoadjuvant regimen: paclitaxel plus cisplatin. It was hypothesized that this new neoadjuvant chemotherapy followed by surgery and chemoradiation therapy would be well tolerated and would have a high curative resection rate.
- Detailed Description
OBJECTIVES:
Primary objective: To evaluate the tolerability and toxicity of neoadjuvant cisplatin plus paclitaxel and postoperative chemoradiation therapy with fluorouracil plus leucovorin calcium in patients with high-risk gastric cancer.
Secondary objectives: To assess the pathologic response of gastric tumors to neoadjuvant cisplatin plus paclitaxel chemotherapy, and preliminarily assess the patterns of failure and disease free and overall survival.
OUTLINE: Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Patients are followed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter.
PROJECTED ACCRUAL: Approximately 30-42 patients will be accrued over 18 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
-
Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction
-
Localized cancer that is potentially curable by surgery (T2, N1-2, M0 or T3-4, any N, M0)
-
No metastatic cancer to the ovaries
-
Age: 18 and over
-
Easter Cooperative Oncology Group (ECOG) performance status 0-2
-
White blood cell (WBC) count at least 4,000 cells/mm3
-
Platelet count at least 150,000/mm3
-
Bilirubin less than 2 mg/dL
-
Creatinine no greater than 1.5 mg/dL
-
Creatinine clearance greater than 50 mL/min
-
Caloric intake must be at least 1500 kcal/day
-
No prior history of cancer within the past 5 years except for basal cell carcinoma of the skin or in situ carcinoma of the cervix
-
No prior radiation therapy, except for skin cancer
-
Fertile patients must use adequate contraception
-
Met criteria for re-registration after surgery
- T1N1-2M0, T2N1-2M0 or T3-4NanyM0 at time of initial re-registration.
- No evidence of metastatic disease from postoperative pathologic staging.
- ECOG performance status of 0, 1, or 2 at re-registration
- Curative resection performed
- Re-registered 4 - 6 weeks from the date of surgery
- WBC ≥ 4000 cells/mm³, platelets ≥ 150,000/mm³, creatinine ≤ 1.5 mg/dl or creatinine clearance of > 50 ml/min (measured or calculated) and total serum bilirubin < 2 mg/dl, all within four weeks prior to re-registration
- Prior chemotherapy
- Clinically significant auditory impairment
- Significant heart disease
- Pregnant or lactating
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Arm radiation therapy Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Experimental Arm paclitaxel Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Experimental Arm surgery Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Experimental Arm leucovorin calcium Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Experimental Arm cisplatin Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment. Experimental Arm fluorouracil Patients receive 3 courses of preoperative neoadjuvant chemotherapy given on day 1 every 21 days. Courses consist of an intravenous infusion of cisplatin and a 3 hour intravenous infusion of paclitaxel on day 1. Patients then undergo surgery for tumor removal on day 63, followed 4-6 weeks later by one course of daily intravenous bolus leucovorin calcium and fluorouracil for 5 days. Chemotherapy is repeated 4-6 weeks later for the first 4 days of week 1 and the last 3 days of week 5 of radiation therapy given 5 days a week for 5 weeks. Patients receive two more courses, 4 weeks apart, of fluorouracil and leucovorin calcium for 5 days 4-6 weeks after completing radiation treatment.
- Primary Outcome Measures
Name Time Method Grade 3 or Higher Toxicity Incidence on Step 1 assessed at the end of every cycle (cycle=21 days) during treatment (3 cycles in total) Incidence is defined as proportion of patients with any grade 3 or higher treatment-related toxicities among all treated patients.
- Secondary Outcome Measures
Name Time Method Overall Survival assessed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter up to year 10 Overall survival was defined as the time from registration to death, where a subject was censored on date of last record alive.
Best Confirmed Response to Neoadjuvant Therapy Assessed at surgery time (surgery performed during week 8-10 after registration to the study) Response was based on pathology at surgery. A patient achieved complete response if no gross or microscopic tumor were identified with the surgical specimen and nodal tissue. Stable response was defined as a response that did not qualify as complete response or progressive disease (PD), where PD indicated metastatic spread. Best confirmed response rate was defined as the proportion of patients with complete response (CR). A patient was considered unevaluable if the patient did not have surgery, the pathologist did not examine at least 15 lymph nodes, or the pathology report was unavailable.
Progression Free Survival assessed every month for the first 3 months, every 3 months for the next 21 months, every 6 months for the next year, and annually thereafter up to year 10 Progression-free survival (PFS) was defined as time from registration until progression, recurrence, or death, whichever occurred first. If date of death occurred beyond three months from the date of last disease assessment, then PFS was censored at date of last disease assessment. Patients who were alive and progression-free were censored at the date of last disease evaluation.
Trial Locations
- Locations (30)
New England Medical Center Hospital
🇺🇸Boston, Massachusetts, United States
CCOP - Colorado Cancer Research Program, Inc.
🇺🇸Denver, Colorado, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Veterans Affairs Medical Center - Indianapolis (Roudebush)
🇺🇸Indianapolis, Indiana, United States
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
🇺🇸Nashville, Tennessee, United States
Veterans Affairs Medical Center - Lakeside Chicago
🇺🇸Chicago, Illinois, United States
CCOP - Cedar Rapids Oncology Project
🇺🇸Cedar Rapids, Iowa, United States
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
🇺🇸Chicago, Illinois, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Somerset Medical Center
🇺🇸Somerville, New Jersey, United States
University of Pennsylvania Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
CCOP - Toledo Community Hospital Oncology Program
🇺🇸Toledo, Ohio, United States
Raritan Bay Medical Center
🇺🇸Perth Amboy, New Jersey, United States
Albert Einstein Comprehensive Cancer Center
🇺🇸Bronx, New York, United States
Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Veterans Affairs Medical Center - Milwaukee (Zablocki)
🇺🇸Milwaukee, Wisconsin, United States
CCOP - Evanston
🇺🇸Evanston, Illinois, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
CCOP - Ann Arbor Regional
🇺🇸Ann Arbor, Michigan, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
University of Rochester Cancer Center
🇺🇸Rochester, New York, United States
CCOP - MainLine Health
🇺🇸Wynnewood, Pennsylvania, United States
CCOP - Marshfield Medical Research and Education Foundation
🇺🇸Marshfield, Wisconsin, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
CCOP - Ochsner
🇺🇸New Orleans, Louisiana, United States