A Phase I/II Study to Evaluate Safety and Efficacy in Patients Who Have Resectable Esophageal Cancer and Are Treated With Neoadjuvant Cisplatin, Irinotecan (CPT-11) ZD1839 (IRESSA), and Radiotherapy Followed by Surgical Resection
18 Years
N/A
Both
Esophageal Cancer
Trial Information
A Phase I/II Study to Evaluate Safety and Efficacy in Patients Who Have Resectable Esophageal Cancer and Are Treated With Neoadjuvant Cisplatin, Irinotecan (CPT-11) ZD1839 (IRESSA), and Radiotherapy Followed by Surgical Resection
OBJECTIVES:
Primary
- Evaluate the pathologic response (complete and partial) in patients with resectable
esophageal or gastroesophageal junction cancer treated with neoadjuvant gefitinib,
cisplatin, irinotecan hydrochloride, and radiotherapy followed by surgical resection.
Secondary
- Assess the safety and toxicity of this regimen in these patients.
- Evaluate objective tumor response in patients treated with this regimen.
- Determine the rate of complete resection in patients treated with this regimen.
- Determine surgical morbidity and mortality in patients treated with this regimen.
OUTLINE: This is an open-label study.
- Induction phase: Patients receive oral gefitinib once daily on days 1-14. Patients with
stable or responding disease proceed to neoadjuvant chemoradiotherapy.
- Neoadjuvant chemoradiotherapy: Patients receive gefitinib as in the induction phase
beginning in week 4 and continuing through the last day of radiotherapy. Patients also
receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over 30 minutes on
days 22, 29, 43, and 50 and undergo radiotherapy once daily, 5 days a week, for 5 weeks
(total of 25 doses).
- Surgery: Within 4-8 weeks after completion of neoadjuvant chemoradiotherapy, patients
with stable or responding disease undergo an esophagectomy and lymph node dissection.
Patients with a progressive or unresectable disease are removed from the study.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma (AC) or squamous cell carcinoma of the
esophagus
- AC of the gastroesophageal junction allowed
- Tumor must be considered surgically resectable (T1-3, NX)
- No early-stage cancer (T1, N0)
- The following lymph node (LN) criteria are considered acceptable:
- Regional thoracic LN metastases (N1)
- LN metastases levels 15 to 20 measured as ≤ 1.5 cm by CT scan
- Supraclavicular LN not palpable on clinical examination measured as ≤ 1.5 cm by
CT scan
- No distant metastases (M0)
PATIENT CHARACTERISTICS:
- Platelet count ≥ 100,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Creatinine clearance ≥ 50 mL/min
- Creatinine serum level ≤ CTC grade 2
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- AST < 3 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment
- No known severe hypersensitivity to gefitinib or any of its excipients
- No evidence (except asymptomatic chronic stable radiographic changes) of clinically
active interstitial lung disease
- No pulmonary fibrosis, Gilbert's disease, uncontrolled diabetes mellitus, or unstable
angina
- No New York Heart Association class III or IV heart disease
- No other concurrent malignancies or malignancies diagnosed within the past 5 years
except basal cell carcinoma or carcinoma in situ of the cervix
- No serious active or uncontrolled infection, systemic disease, psychiatric illness,
or other medical condition that would preclude study participation
- No evidence of any significant clinical disorder or laboratory finding that would
preclude study participation
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy for esophageal cancer
- No prior radiotherapy that would overlap the study treatment fields
- Recovered from prior major surgery
- No nonapproved or investigational drugs within the past 30 days
- No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or
Hypericum perforatum (St. John's wort)
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathological response (complete and partial) post-operatively
Safety Issue:
No
Principal Investigator
Andrew Ko, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000456200
NCT ID:
NCT00290719
Start Date:
November 2005
Completion Date:
March 2008
Related Keywords:
- Esophageal Cancer
- adenocarcinoma of the esophagus
- squamous cell carcinoma of the esophagus
- stage II esophageal cancer
- stage III esophageal cancer
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
