Radiotherapy,Chemotherapy,Before and After Surgery in Advanced Esophageal or Gastroesophageal Junction Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00258323
Recruitment Status : Completed
First Posted : November 24, 2005
Last Update Posted : September 30, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

November 22, 2005
November 24, 2005
September 30, 2015
October 2005
July 2007   (Final data collection date for primary outcome measure)
  • Survival at 1 year [ Time Frame: 1 year ]
    Survival at 1 year
  • Distant metastatic control at 1 year [ Time Frame: 1 year ]
    Distant metastatic control at 1 year
Not Provided
Complete list of historical versions of study NCT00258323 on Archive Site
  • Response rate at 6 weeks [ Time Frame: 6 weeks ]
    Response rate at 6 weeks
  • Toxicity of induction chemoradiotherapy and gefitinib as measured by CTC version 2.0 at 6 weeks [ Time Frame: 6 weeks ]
    Toxicity of induction chemoradiotherapy and gefitinib as measured by CTC version 2.0 at 6 weeks
  • Toxicity of maintenance gefitinib as measured by CTC version 2.0 every 8 weeks after the completion of radiotherapy [ Time Frame: 8 weeks ]
    Toxicity of maintenance gefitinib as measured by CTC version 2.0
Not Provided
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Radiotherapy,Chemotherapy,Before and After Surgery in Advanced Esophageal or Gastroesophageal Junction Cancer
A Phase II Trial of Pre- and Postoperative Chemoradiotherapy and ZD1839 (IRESSA) Followed by Maintenance ZD1839 in Patients With Locoregionally Advanced Esophageal and Gastroesophageal Junction Carcinoma

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Cisplatin and fluorouracil may also make tumor cells more sensitive to radiation therapy. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with combination therapy and gefitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with combination chemotherapy and gefitinib before and after surgery works in treating patients with advanced esophageal or gastroesophageal junction cancer.



  • Determine the activity of gefitinib, in terms of median survival and distant metastatic disease control, in patients treated with neoadjuvant and adjuvant cisplatin, fluorouracil, and radiotherapy who are undergoing surgery for esophageal and gastroesophageal junction cancer.


  • Determine the pathologic complete and partial response rate in patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients and in patients who are disease free and receiving long-term maintenance gefitinib.


  • Preoperative regimen: Patients undergo radiotherapy twice a day during days 1-12 (for a total of 10 treatment days). Patients receive fluorouracil IV continuously and cisplatin IV continuously on days 1-4. Patients also receive oral gefitinib once daily on days 1-28. At 6 weeks, patients with locoregionally confined disease undergo surgical resection and then proceed to the postoperative regimen. Patients with a medical contraindication to surgery proceed directly to the postoperative regimen.
  • Postoperative regimen: Beginning 4-10 weeks after surgery or 6 weeks after completing the first course of therapy, patients undergo radiotherapy and receive fluorouracil and cisplatin as in the preoperative regimen.
  • Maintenance regimen: Patients receive oral gefitinib beginning on day 1 of the postoperative regimen and continuing for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Esophageal Cancer
  • Drug: cisplatin
    20mg/m2d/IV continuous infusion x days
    Other Name: CDDP
  • Drug: fluorouracil
    1000mg/m2/d IV continuous infusion x 4 days
    Other Name: 5 FU
  • Drug: Iressa
    250mg po qd days 1-28 then x 2 years
    Other Name: ZD 1839
  • Procedure: conventional surgery
    conventional surgery
  • Radiation: radiation therapy
    150 cGy bid
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
February 2010
July 2007   (Final data collection date for primary outcome measure)


  • Histologically or cytologically confirmed squamous cell carcinoma, adenocarcinoma, or large cell undifferentiated cancer of the esophagus or gastroesophageal junction

    • T3, N1, or M1a disease only
    • The following types are not allowed:

      • Small cell undifferentiated carcinomas, lymphomas, or sarcomas
      • Small cell or mixed small cell/non-small cell histology
  • No evidence of distant hematogenous tumor metastases (M1b)
  • No malignant pleural effusions


Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • WBC > 3,500/mm^3
  • Platelet count > 100,000/mm^3


  • Alkaline phosphatase < 2 times normal
  • AST < 2 times normal
  • No unstable or uncompensated hepatic disease


  • Creatinine ≤ 2.0 mg/dL
  • Calcium normal
  • No unstable or uncompensated renal disease


  • No unstable or uncontrolled angina
  • No unstable or uncompensated cardiac disease


  • See Disease Characteristics
  • No limitations to pulmonary function that would preclude study participation
  • No evidence of clinically active interstitial lung disease (asymptomatic patients with chronic stable radiographic changes are allowed)
  • No unstable or uncompensated respiratory disease


  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No evidence of severe or uncontrolled systemic disease
  • No other uncontrolled malignancy
  • No active infection
  • No known severe hypersensitivity to gefitinib or any of its excipients


Biologic therapy

  • No prior immunotherapy for this cancer


  • No prior chemotherapy for this cancer


  • No prior radiotherapy for this cancer


  • Recovered from any prior oncologic or other major surgery
  • No prior surgical resection for this cancer
  • No concurrent ophthalmic surgery


  • No prior photodynamic therapy for this cancer (prior laser treatments are acceptable)
  • More than 30 days since prior unapproved or investigational drug
  • No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA043703 ( U.S. NIH Grant/Contract )
CCF-5848 ( Other Identifier: Cleveland Clinic IRB )
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Not Provided
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: David J. Adelstein, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP