A Pilot Study of the Biologic Efficacy and Safety of the Addition of Celecoxib to a Program of Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for the Treatment of Esophageal Cancer
18 Years
N/A
Both
Esophageal Cancer
Trial Information
A Pilot Study of the Biologic Efficacy and Safety of the Addition of Celecoxib to a Program of Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for the Treatment of Esophageal Cancer
OBJECTIVES:
Primary
- To measure the rates of cellular apoptosis and proliferation at baseline and during
chemoradiotherapy with and without celecoxib using biopsy samples from patients with
stage II, III, or IV esophageal cancer.
- To determine if an acceptable rate of pathologic complete remission can be achieved in
a subset of patients with potentially resectable esophageal cancer.
Secondary
- To assess the safety of the addition of daily celecoxib to chemoradiotherapy.
- To estimate the median overall survival in a subset of patients with resectable
disease.
- To quantitate expression of cyclooxygenase (COX)-2 and formation of prostaglandin E2
(PGE2) in patients with esophageal cancer.
- To assess the ability of celecoxib to decrease formation of PGE2 in tumor tissue by
measuring pre- and post-treatment tumor concentrations of PGE2.
- To quantitate downstream effects of inhibition of COX-2 function in the setting of
treatment with chemotherapy.
- To measure the radiographic response rate in patients with unresectable esophageal
cancer.
OUTLINE: This is a multicenter study. Patients are sequentially enrolled into 1 of 2
treatment groups.
- Group 1: Patients receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over
90 minutes on days 1, 8, 22, 29, 43, 50, 64, and 71. Patients also undergo radiotherapy
once daily 5 days a week for 5 weeks beginning on day 43.
- Group 2: Patients receive chemoradiotherapy as in group 1. Patients also receive oral
celecoxib twice daily beginning 3 days before the initiation of chemotherapy and
continuing until the completion of chemoradiotherapy.
In both groups, patients with potentially resectable disease undergo surgery no more than 12
weeks after completion of chemoradiotherapy.
Endoscopic tumor biopsy specimens are collected at baseline and on day 3 of radiotherapy.
Samples are analyzed for cyclooxygenase (COX)-2 gene and protein expression; PGE2 secretion;
apoptotic activity; caspase-3 activation; cytochrome c translocation; VEGF mRNA
quantitation; and cellular proliferation. Laboratory techniques used include RT-PCR, IHC,
enzyme immunoassay, TUNEL assay, colorimetric assay, and northern blotting.
After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 34 patients (8-10 in group 1 and 24 in group 2) will be
accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Biopsy proven squamous cell carcinoma or adenocarcinoma of the esophagus
- Lesions including the gastroesophageal junction allowed provided the tumor
involves less than 2 cm of gastric cardia
- Meets 1 of the following criteria:
- Clinical stage II, III, or IV disease AND planning to receive chemoradiotherapy
either for preoperative or palliative indications (group 1)
- Suitable candidate for bimodality (palliative intent) or trimodality
(curative intent) therapy
- Clinical stage II or III disease AND candidate to receive chemoradiotherapy for
preoperative indication followed by planned esophagectomy or esophagogastrectomy
(group 2)
- Suitable candidate for trimodality (curative intent) therapy
- No tracheoesophageal fistula on bronchoscopy
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months (group 1)
- Not pregnant
- Adequate nutrition
- WBC ≥ 4,000/μL
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Serum creatinine ≤ 1.5 mg/dL
- Bilirubin ≤ 1.5 mg/dL
- No other prior or concurrent malignancy other than curatively treated carcinoma in
situ of the cervix; localized prostate cancer that was previously treated with local
therapy more than 2 years ago with a PSA of less than 4 ng/mL; basal cell carcinoma
of the skin; or superficial transitional cell carcinoma of the bladder
- Patients who have had a prior malignancy are eligible if they have been free of
disease for ≥ 5 years
- No serious medical or psychiatric illnesses that would preclude giving informed
consent or otherwise limit survival to less than 2 years
- No history of known NSAID-induced gastrointestinal bleeding
- No current peptic ulcer disease
- No active coronary artery disease
- No myocardial infarction or cerebrovascular accident within the past 3 months
- No history of refractory congestive heart failure or cardiomyopathy
PRIOR CONCURRENT THERAPY:
- More than 1 week since prior major surgery (group 1)
- More than 2 weeks since prior major surgery (group 2)
- No prior chemotherapy or radiotherapy
- More than 30 days since prior cyclooxygenase-2 inhibitors (selective or
non-selective), including, but not limited to, any of the following:
- Acetylsalicylic acid (aspirin)
- Piroxicam
- Diclofenac
- Meloxicam
- Indomethacin
- Fenoprofen
- Sulindac
- Flurbiprofen
- Tolmetin
- Ibuprofen
- Celecoxib
- Ketoprofen
- Rofecoxib
- Ketoprofen ER
- Valdecoxib
- Naproxen
- Meclofenamate
- Oxaprozin
- Mefenamic acid
- Etodolac
- Nabumetone
- Ketorolac
- No concurrent seizure medications
- No concurrent amifostine or other such agents
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rates of cellular apoptosis and proliferation
Outcome Description:
Measure the rates of cellular apoptotis and proliferation in esophageal cancers from biopsy samples pre-study and during chemoradiation with and without celecoxib therapy
Outcome Time Frame:
5 weeks
Safety Issue:
Yes
Principal Investigator
Bert H. O'Neil, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UNC Lineberger Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
LCCC 0203
NCT ID:
NCT00520091
Start Date:
March 2005
Completion Date:
September 2010
Related Keywords:
- Esophageal Cancer
- adenocarcinoma of the esophagus
- squamous cell carcinoma of the esophagus
- stage II esophageal cancer
- stage III esophageal cancer
- stage IV esophageal cancer
- Esophageal Diseases
- Esophageal Neoplasms
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