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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00052910
First received: January 24, 2003
Last updated: June 23, 2015
Last verified: June 2015
  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 Alliance for Clinical Trials in Oncology:

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
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
  1. Required Tumor Parameters

    1.1 Patients must have histologically diagnosed adenocarcinoma of the stomach or gastroesophageal junction. Adenocarcinomas of the esophagus that are not involving the gastroesophageal junction are not eligible.

    1.2 Patients must have had en bloc resection of all known tumor. The surgical resection must have been done with a curative intent.

    1.3 Patients must have tumor extension beyond muscularis propria and/or nodal involvement without evidence of M1 disease.

    • Patients can have stages IB if there is evidence of either node-positive (N1) disease or tumor extension beyond the muscularis propria (i.e., T1, N1, M0 patients are eligible but patients with T2, N0, M0 are allowed only if there is extension beyond the muscularis propria).
    • Patients can have stages II, IIIA, IIIB or stage IV with M0 (i.e., T4N2M0).
    • Stages 0, IA, or any stage with M1 are not allowed. (see Appendix I for TNM staging guide).

    1.4 Patients with known unresected cancer, recurrent cancer, microscopic evidence of tumor at the distal or proximal line of stomach resection, noncontiguous resection of tumor, or M1 (metastatic) disease are ineligible.

  2. Prior Therapy

    2.1 No prior therapy (except hormonal or biologic) for other malignancies is allowed except for adequately treated basal cell or squamous cell skin cancer, noninvasive carcinoma in situ which has been fully resected, or other cancer for which the patient has been disease free for five years.

    2.2 Patients who have had any previous chemotherapy or radiotherapy are ineligible.

  3. Patient Characteristics

    3.1 Patients must have an ECOG (CTC) performance status of 0, 1 or 2.

    3.2 Patients are required to have an adequate total caloric intake to allow them to maintain their post-surgical body weight. Patients must have documentation of stable weight (or less than 2 pounds weight loss) for at least one week prior to registration.

    3.3 All patients must be evaluated by a radiation oncologist (prior to enrollment) to ensure that the patient is an appropriate candidate for radiation therapy.

    3.4 Patients may not have unilateral renal function (only one functioning kidney) as determined by CT scan with contrast, urogram, renal scan, or other study.

    3.5 Pregnant or lactating women may not participate. Men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method or practice abstinence while in this study.

    • The effects of therapeutic radiotherapy are known to be teratogenic.
    • The effects of Epirubicin, Cisplatin, and 5-FU on a developing human fetus at the recommended therapeutic dose are less well known.
    • For this reason and because DNA alkylating agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.
    • Should a woman become pregnant or suspect she is pregnant while participating on this study, she should inform her treating physician immediately. Because the risk of toxicity in nursing infants secondary to Epirubicin, Cisplatin, and 5-FU treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued.

    3.6 Patients with any of the following cardiac conditions are ineligible:

    • Uncontrolled high blood pressure
    • Unstable angina
    • Symptomatic congestive heart failure
    • Myocardial infarction < 6 months prior to registration
    • Serious uncontrolled cardiac arrhythmia
    • New York Heart Association classification III or IV.

    3.7 No uncontrolled serious medical or psychiatric illness which would prevent compliance with treatment or adequate informed consent.

    3.8 Patients with active infectious process are ineligible.

    3.9 Patients with grade 2 or greater peripheral neuropathy at baseline are ineligible.

  4. Required Initial Laboratory Values:

    • Granulocytes ≥ 1,500/μl
    • Platelet count ≥ 100,000/μl
    • Creatinine ≤ 1.5 mg/dl
    • Bilirubin ≤ 2.0 mg/dl
    • AST ≤ 3x upper limits of normal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052910

  Show 535 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Charles S. Fuchs, MD Dana-Farber Cancer Institute
  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: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00052910     History of Changes
Other Study ID Numbers: CALGB-80101, U10CA031946, CDR0000258787
Study First Received: January 24, 2003
Last Updated: June 23, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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:
Esophageal Neoplasms
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases
Epirubicin
Fluorouracil
Levoleucovorin
Antibiotics, Antineoplastic
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 02, 2015