Surgery With or Without Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00003118
First received: November 1, 1999
Last updated: July 1, 2016
Last verified: June 2016
  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. It is not yet known whether surgery is more effective with or without chemotherapy and radiation therapy for cancer of the esophagus.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy and radiation therapy in treating patients who have cancer of the esophagus that can be surgically removed.


Condition Intervention Phase
Esophageal Cancer
Drug: cisplatin
Drug: fluorouracil
Procedure: surgical procedure
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Phase III Trial Comparing Trimodality Therapy (Cisplatin, 5-FU, Radiotherapy, and Surgery) to Surgery Alone for Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Overall survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: October 1997
Study Completion Date: March 2000
Primary Completion Date: March 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy + Radiation + Surgery Drug: cisplatin Drug: fluorouracil Procedure: surgical procedure Radiation: radiation therapy
Active Comparator: Surgery Procedure: surgical procedure

Detailed Description:

OBJECTIVES: I. Compare overall five-year survival rates and treatment failures in patients receiving neoadjuvant cisplatin (CDDP) plus fluorouracil (5-FU) with concomitant radiotherapy followed by surgical resection versus patients receiving surgery alone. II. Assess and compare the toxicities of each approach. III. Compare the incidence and pattern of local (gastric or esophageal bed or regional lymph nodes) and distant (supraclavicular lymph node, liver, peritoneal carcinomatosis, or lung, brain, etc.) recurrence. IV. Evaluate the prognostic ability of noninvasive and minimally invasive pretreatment staging with regard to survival and recurrence. V. Evaluate the ability of preresection adjuvant chemotherapy with concomitant radiation therapy to render tumors to lower stages. VI. Evaluate the impact of lymph nodes on survival and recurrence.

OUTLINE: This a two arm, randomized study. Patients are stratified by: cell type of cancer (squamous cell vs adenocarcinoma); lymph nodes (positive vs negative); and stage (invasive vs noninvasive). Patients in arm I undergo chemotherapy and radiotherapy within 24 hours of each other. Chemotherapy consists of cisplatin (CDDP) by bolus IV infusion over 30 minutes on day 1 and again on day 29. Fluorouracil (5-FU) is administered by continuous IV infusion for 4 days (on days 1-4 and 29-32) after completion of cisplatin. Radiotherapy is administered on days 1-5, 8-12, 15-19, 22-26, and 29-33, with a boost on days 36-38. If there is no disease progression or unresectable disease, surgery is performed within 3-8 weeks following completion of therapy. Patients in arm II undergo surgery alone no later than 6 weeks postrandomization. Patients are followed at least every 3 months for two years, then every 6 months for the next two years, and annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Patients with histologically documented untreated squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastro-esophageal junction and with less than 2 cm distal spread into the gastric cardia were eligible.
  2. No evidence of distant metastatic disease by history and physical examination
  3. Upper endoscopy with biopsy, computed tomography (CT) of the chest and upper abdomen, and pulmonary function studies are required.
  4. Bone scan is required for alkaline phosphatase more than 3X the institutional normal value.
  5. Bronchoscopy is required if the primary tumor was adjacent to the trachea or left main stem bronchus.
  6. Patients are required to have:

    • granulocyte counts ≥1,800/mL
    • platelet count ≥ 100,000/mL
    • creatinine clearance ≥ 50 mL/min
  7. Esophageal ultrasound (EUS) and preresection staging by thoracoscopy (ts) and laparoscopy/minilaparotomy (ls), including biopsy of celiac axis and lesser curvature are recommended
  8. Tumors must be considered surgically resectable (T1-3, NX), including regional thoracic lymph node (N1) metastases.
  9. Patients with supraclavicular lymph nodes measuring ≤ 1.5 cm by CT (not palpable) are eligible.
  10. Patients with lymph node metastases to levels 15 to 20 (predominantly celiac axis and paracardial nodes) ≤1.5 cm by CT.
  11. Patients may not have previously received chemotherapy or radiation therapy for this tumor or any radiation therapy that would overlap the radiation fields required for this malignancy.
  12. Patients with previous malignancies are eligible if more than 5 years had elapsed from diagnosis without evidence of tumor recurrence.
  13. There can be no other serious illness that would limit survival to less than 2 years, or psychiatric condition that would prevent compliance with treatment or informed consent. Patients with uncontrolled or severe cardio- vascular disease,pulmonary disease, oractive infections are excluded.
  14. Pregnant patients are excluded.
  15. Informed consent is required for all patients.
  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: NCT00003118

  Show 38 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Mark Krasna, MD Jersey Shore University Medical Center
  More Information

Publications:
Krasna M, Tepper JE, Niedzwiecki D, et al.: Trimodality therapy is superior to surgery alone in esophageal cancer: results of CALGB 9781. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-4, 2006.
Tepper JE, Krasna M, Niedzwiecki D, et al.: Superiority of trimodality therapy to surgery alone in esophageal cancer: results of CALGB 9781. [Abstract] J Clin Oncol 24 (Suppl 18): A-4012, 2006.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00003118     History of Changes
Other Study ID Numbers: CALGB-9781  U10CA031946  CLB-C9781  E-C9781  NCCTG-C9781  RTOG-9716  CDR0000065873 
Study First Received: November 1, 1999
Last Updated: July 1, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage I esophageal cancer
stage II esophageal cancer
stage III esophageal cancer
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cisplatin
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016