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

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Esophageal Cancer

Treatments

Drug: cisplatin

Radiation: radiation therapy

Procedure: conventional surgery

Drug: fluorouracil

Drug: Iressa

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00258323

CCF-5848 (Other Identifier)

ZENECA-1839/US/0233

P30CA043703 (U.S. NIH Grant/Contract)

CCF5848

Details and patient eligibility

About

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.

Full 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.

Enrollment

80 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)