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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00258323
First received: November 22, 2005
Last updated: October 28, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Drug: cisplatin
Drug: fluorouracil
Drug: Iressa
Procedure: conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Survival at 1 year

  • Distant metastatic control at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Distant metastatic control at 1 year


Secondary Outcome Measures:
  • Response rate at 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Toxicity of maintenance gefitinib as measured by CTC version 2.0


Enrollment: 80
Study Start Date: October 2005
Study Completion Date: February 2010
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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
    Other Name: conventional surgery
    Radiation: radiation therapy
    150 cGy bid
    Other Name: radiation therapy
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

OUTLINE:

  • 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

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

Renal

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

Cardiovascular

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

Pulmonary

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior immunotherapy for this cancer

Chemotherapy

  • No prior chemotherapy for this cancer

Radiotherapy

  • No prior radiotherapy for this cancer

Surgery

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

Other

  • 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)
  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: NCT00258323

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: David J. Adelstein, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00258323     History of Changes
Other Study ID Numbers: CCF5848, P30CA043703, CCF-5848, ZENECA-1839/US/0233
Study First Received: November 22, 2005
Last Updated: October 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

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
Gefitinib
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014