Phase II Study in Operable Adenocarcinoma of the Esophagus to Measure Response Rate and Toxicity of Preoperative Combined Modality Paclitaxel (Taxol®, Bristol-Myers Squibb), Cisplatin (Platinol®, Abbott Laboratories), ZD1839 (IRESSA®) and Radiotherapy Followed by Postoperative ZD1839
18 Years
80 Years
Both
Esophageal Cancer
Trial Information
Phase II Study in Operable Adenocarcinoma of the Esophagus to Measure Response Rate and Toxicity of Preoperative Combined Modality Paclitaxel (Taxol®, Bristol-Myers Squibb), Cisplatin (Platinol®, Abbott Laboratories), ZD1839 (IRESSA®) and Radiotherapy Followed by Postoperative ZD1839
OBJECTIVES:
Primary
- Determine the pathologic complete response rate in patients with resectable, locally
advanced adenocarcinoma of the esophagus or gastroesophageal junction treated with
neoadjuvant paclitaxel, cisplatin, gefitinib, and radiotherapy followed by surgery and
adjuvant gefitinib.
Secondary
- Determine the survival of patients treated with this regimen.
- Determine the safety and tolerability of this regimen in these patients.
- Determine time to disease progression in patients treated with this regimen.
- Determine the plasma pharmacokinetics of unbound gefitinib in these patients.
- Conduct exploratory studies to determine if EGFR pathway component expression and
activation correlates with response to therapy and survival of these patients.
- Determine if treatment with gefitinib alters the EGFR pathway in these patients.
OUTLINE: This is a prospective study.
- Neoadjuvant therapy: Patients receive oral gefitinib beginning 14 days prior to the
start of chemoradiotherapy and continuing until 7 days prior to surgery (10-12 weeks).
Patients also receive paclitaxel IV over 1 hour and cisplatin IV over 2-3 hours on days
1, 8, 15, 22, and 29. Patients also undergo radiotherapy 5 days a week for 5 weeks.
- Surgery: Patients undergo surgical resection 4-6 weeks after the completion of
neoadjuvant therapy.
- Adjuvant therapy: Patients receive gefitinib once a day beginning 2-8 weeks after
surgery and continuing for up to 1 year in the absence of disease progression or
unacceptable toxicity.
Blood samples are obtained at baseline and periodically during study for pharmacokinetic
studies. Tumor tissue samples are obtained by core biopsy at baseline for biomarker
correlative studies. Samples are analyzed by IHC to measure expression and activation of
EGFR-signaling pathway biomarkers in pretreatment esophageal tumor tissue, including EGFR
and phosphorylated (p)-EGFR, ERK and p-ERK, Akt and p-Akt, p70s6k and p-p70s6k, and p27.
After completion of study therapy, patients are followed periodically for at least 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction
meeting the following criteria:
- Newly diagnosed disease
- Surgically resectable tumor
- Primary esophageal tumor < 20 cm below the incisors
- Tumor extending ≤ 2 cm into the cardia
- Stage T2-3, N0-1, M0-1a tumor, as determined by imaging studies and biopsy
- Documentation by endoscopic ultrasound, endoscopy, and CT scan of the chest and
abdomen required
- Any lesion suspicious for metastasis must be biopsied
- M1a disease (i.e., celiac nodal metastasis) is allowed if other eligibility
criteria are met
- T4 disease (i.e., involvement of the pleura, pericardium, or diaphragm) allowed
provided it is considered resectable
- No CNS metastasis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Granulocyte count > 1,000/mm³
- Platelet count > 75,000/mm³
- Creatinine clearance > 60 mL/min
- Total bilirubin < 1.5 mg/dL
- No concurrent illness likely to preclude protocol therapy or surgical resection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy
- No known severe hypersensitivity to gefitinib or any of its excipients
- No evidence of severe or uncontrolled systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease)
- No evidence of other significant clinical disorder or laboratory finding that would
preclude study participation
- No evidence of clinically active interstitial lung disease
- Patients with chronic, stable radiographic changes that are asymptomatic are
eligible
- No other prior or concurrent malignancy except basal cell or squamous cell skin
cancer, cervical cancer, or any other curatively treated malignancy from which the
patient has been disease-free and has a survival prognosis of > 5 years
- No preexisting peripheral neuropathy > grade 1
PRIOR CONCURRENT THERAPY:
- No incomplete healing from prior oncologic or other major surgery
- No prior chemotherapy, radiotherapy, or surgery for this cancer
- Endoscopy with biopsy and dilation is allowed
- More than 30 days since prior nonapproved or investigational drugs
- No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or
Hypericum perforatum (St. John's wort)
- No concurrent oral retinoids
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologic complete response rate to the neoadjuvant regimen
Outcome Time Frame:
5 years
Safety Issue:
No
Principal Investigator
Arlene A. Forastiere, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
JHOC-J0386, CDR0000549896
NCT ID:
NCT00493025
Start Date:
April 2005
Completion Date:
July 2011
Related Keywords:
- Esophageal Cancer
- adenocarcinoma of the esophagus
- stage II esophageal cancer
- stage III esophageal cancer
- stage IV esophageal cancer
- Adenocarcinoma
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
