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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00052910
First received: January 24, 2003
Last updated: April 10, 2012
Last verified: April 2011
  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
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease free survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 546
Study Start Date: December 2002
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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 to 6 weeks. Patients rest for 28-35 days between course 2 and 3.
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Radiation: radiation therapy
Given 5 days a week for 5 weeks
Experimental: 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 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
Radiation: 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
  • All patients must be evaluated by a radiation oncologist prior to enrollment to ensure patient is appropriate for radiotherapy

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 535 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 Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
Publications:
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.

Responsible Party: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00052910     History of Changes
Other Study ID Numbers: CDR0000258787, U10CA031946, CALGB-80101, NCCTG-CALGB-80101, ECOG-CALGB-80101
Study First Received: January 24, 2003
Last Updated: April 10, 2012
Health Authority: United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:
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

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Cisplatin
Epirubicin
Fluorouracil
Leucovorin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 20, 2014