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Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00052910
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Gastric Cancer
Drug: cisplatin
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: leucovorin calcium
Procedure: radiation therapy
Phase III

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer
Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Cisplatin Fluorouracil Epirubicin hydrochloride Epirubicin Calcium gluconate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 824
Study Start Date: December 2002
Estimated Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
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.
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Procedure: radiation therapy
Given 5 days a week for 5 weeks
Arm II: Experimental
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 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.
Drug: cisplatin
Given IV
Drug: epirubicin hydrochloride
Given IV
Drug: fluorouracil
Given IV
Procedure: radiation therapy
Given 5 days a week for 5 weeks

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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (adenocarcinoma of the esophagus must involve the gastroesophageal junction) meeting the following criteria:

    • Tumor extension beyond muscularis propria and/or nodal involvement without evidence of M1 disease
    • Stage II, IIIA, IIIB, or IV (T2, N2, M0)
    • Stage IB (T1, N1, M0; T2, N0, M0 allowed if extension beyond muscularis propia)
  • Prior en bloc resection, with curative intent, of all known tumor

    • No microscopic evidence of tumor at the line of resection
    • No noncontiguous resection
  • No known unresected or recurrent disease at the distal or proximal line of stomach resection
  • No metastatic disease

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2.0 mg/dL
  • AST no greater than 3 times upper limit of normal

Renal

  • Creatinine no greater than 1.5 mg/dL
  • No unilateral renal function

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No uncontrolled high blood pressure
  • No unstable angina
  • No symptomatic congestive heart failure
  • No serious uncontrolled cardiac arrhythmia
  • No New York Heart Association class III or IV heart disease
  • No cardiac disease resulting in marked limitation or inability of physical activity

Other

  • Stable weight for at least one week before study
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or fully resected noninvasive carcinoma in situ
  • No other uncontrolled serious medical condition or psychiatric illness that would preclude study entry
  • No active infection
  • No peripheral neuropathy grade 2 or greater

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior biologic therapy allowed

Chemotherapy

  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Prior hormonal therapy allowed
  • No concurrent hormonal therapy except the following:

    • Steroids for adrenal failure
    • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
    • Intermittent dexamethasone as an antiemetic

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  • At least 3 weeks since prior surgery
  • No more than 12 weeks since prior surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00052910

  Show 565 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Charles S. Fuchs, MD Dana-Farber Cancer Institute
Study Chair: Steven R. Alberts, MD Mayo Clinic
Study Chair: Daniel G. Haller, MD University of Pennsylvania
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.

Study ID Numbers: CDR0000258787, CALGB-80101, NCCTG-CALGB-80101, ECOG-CALGB-80101
Study First Received: January 24, 2003
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00052910  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I gastric cancer
stage II gastric cancer
stage III gastric cancer
adenocarcinoma of the stomach
adenocarcinoma of the esophagus
stage I esophageal cancer
stage II esophageal cancer
stage III esophageal cancer

Study placed in the following topic categories:
Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Leucovorin
Stomach cancer
Epirubicin
Carcinoma
Calcium, Dietary
Digestive System Diseases
Stomach Diseases
Cisplatin
Fluorouracil
Stomach Neoplasms
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases
Adenocarcinoma
Esophageal neoplasm
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Vitamin B Complex
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Vitamins
Therapeutic Uses
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009