NCT00520091

Irinotecan, Cisplatin, and Radiation Therapy With or Without Celecoxib in Treating Patients With Stage II, Stage III, or Stage IV Esophageal Cancer

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy and radiation therapy together with celecoxib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving irinotecan and cisplatin together with radiation therapy with or without celecoxib works in treating patients with stage II, stage III, or stage IV esophageal cancer.

Detailed description

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.

Conditions

• Esophageal Cancer

Interventions

Type	Name	Description
DRUG	CPT- 11	65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery
DRUG	Cisplatin	Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery
DRUG	Celecoxib	400 mg, orally, twice per day beginning on day minus 3 and continue until the end of chemoradiation with CPT-11 and Cisplatin
RADIATION	Radiation	4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks
PROCEDURE	Surgery	Surgery will occur prior to chemoradiation therapy for those patients with resectable disease

Timeline

• Start date: 2005-03-01
• Primary completion: 2006-11-01
• Completion: 2010-09-01
• First posted: 2007-08-23
• Last updated: 2012-05-18