Radiotherapy, Combination Chemotherapy, and Gefitinib Before and After Surgery in Treating Patients With Advanced Esophageal or Gastroesophageal Junction Cancer - Full Text View

Sponsors and Collaborators:	Case Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00258323

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: gefitinib Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Fluorouracil ZD1839

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival at 1 year [ Designated as safety issue: No ]
Distant metastatic control at 1 year [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate at 6 weeks [ Designated as safety issue: No ]
Toxicity of induction chemoradiotherapy and gefitinib as meassured by CTC version 2.0 at 6 weeks [ Designated as safety issue: Yes ]
Toxicity of maintenance gefitinib as measured by CTC version 2.0 every 8 weeks after the completion of radiotherapy [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	October 2005

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

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 nonapproved or investigational drug
No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00258323

Locations

United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

David J. Adelstein, MD

The Cleveland Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000449693, CASE-CCF-5848, ZENECA-1839/US/0233
Study First Received:	November 22, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00258323
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Squamous cell carcinoma
Carcinoma
Epidermoid carcinoma
Digestive System Diseases
Cisplatin

Fluorouracil
Head and Neck Neoplasms
Carcinoma, squamous cell
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Gefitinib
Esophageal neoplasm

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Immunosuppressive Agents
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009