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Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer

Phase 3
Completed
Conditions
Esophageal Cancer
Gastric Cancer
Interventions
Registration Number
NCT00052910
Lead Sponsor
Alliance for Clinical Trials in Oncology
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 with radiation therapy after surgery may kill any remaining tumor cells following surgery. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating stomach or esophageal cancer.

PURPOSE: Randomized phase III trial to compare two different chemotherapy and radiation therapy regimens in treating patients who have undergone surgery for stomach or esophageal cancer.

Detailed Description

OBJECTIVES:

* Compare overall survival in patients with resected gastric adenocarcinoma treated with epirubicin, cisplatin, and infusional fluorouracil (5-FU) vs 5-FU bolus and leucovorin calcium before and after 5-FU plus radiotherapy.

* Compare disease-free survival and local and distant recurrence rates in these patients treated with these regimens.

* Correlate the expression of putative prognostic markers (including TS, ERCC-1, MSI, E-cadherin, EGFR, p27, COX-2, and c-erbB-2) with overall survival of patients treated with these regimens.

* Correlate specific germline polymorphisms related to chemotherapy metabolism and resistance (including UGT2B7 \[epirubicin\], GST \[cisplatin\], ERCCI \[cisplatin\], XRCC1 \[cisplatin\], TS \[5-FU\], DPD \[5-FU\], and EGFR polymorphisms) with treatment-related toxicity and overall survival of these patients.

* Correlate serum levels of insulin-like growth factor-1 (IGF-1), IGF-2, and IGF-binding protein 3 with overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to depth of tumor penetration (T1 or T2 vs T3 vs T4), lymph node involvement (0 vs 1-3), and extent of lymphadenectomy (D1 or D2 vs D0 or unknown). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3, and 4. Courses repeat every 28 days. During course 2, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days between course 2 and 3.

* Arm II: Patients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses.

Patients are followed every 3 months for 2 years, every 4 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 824 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
546
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm Ileucovorin calciumPatients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3, and 4. Courses repeat every 28 days. During course 2, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 to 6 weeks. Patients rest for 28-35 days between course 2 and 3.
Arm Iradiation therapyPatients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3, and 4. Courses repeat every 28 days. During course 2, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 to 6 weeks. Patients rest for 28-35 days between course 2 and 3.
Arm IIepirubicin hydrochloridePatients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses.
Arm IIradiation therapyPatients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses.
Arm IfluorouracilPatients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3, and 4. Courses repeat every 28 days. During course 2, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 to 6 weeks. Patients rest for 28-35 days between course 2 and 3.
Arm IIcisplatinPatients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses.
Arm IIfluorouracilPatients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses.
Primary Outcome Measures
NameTimeMethod
Overall SurvivalFrom study enrollment until death from any cause; up to 3 years

Overall survival is defined as the time from study enrollment to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Secondary Outcome Measures
NameTimeMethod
Disease Free SurvivalFrom the date of study enrollment until death or documented second primary tumor, or cancer recurrence; up to 4 years

Disease free survival is defined as the time from the date of study enrollment to death or documented second primary tumor, or cancer recurrence.The distribution of disease free survival time will be estimated using the method of Kaplan-Meier.

Trial Locations

Locations (531)

Regional Medical Center

🇺🇸

Anniston, Alabama, United States

Providence Cancer Center at Providence Hospital

🇺🇸

Mobile, Alabama, United States

Mayo Clinic Scottsdale

🇺🇸

Scottsdale, Arizona, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

🇺🇸

Fort Smith, Arkansas, United States

Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center

🇺🇸

Jonesboro, Arkansas, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Kaiser Permanente - Deer Valley

🇺🇸

Antioch, California, United States

Providence Saint Joseph Medical Center - Burbank

🇺🇸

Burbank, California, United States

East Bay Radiation Oncology Center

🇺🇸

Castro Valley, California, United States

Scroll for more (521 remaining)
Regional Medical Center
🇺🇸Anniston, Alabama, United States

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