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

NCT ID: NCT00520091

Last Updated: 2012-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2010-09-30

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Induction chemotherapy and chemoradiation without celecoxib

Group Type: ACTIVE_COMPARATOR

CPT- 11

Intervention Type: DRUG

65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery

Cisplatin

Intervention Type: DRUG

Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery

Radiation

Intervention Type: RADIATION

4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks

Surgery

Intervention Type: PROCEDURE

Surgery will occur prior to chemoradiation therapy for those patients with resectable disease

Cohort 2

Induction chemotherapy and chemoradiation with celecoxib

Group Type: EXPERIMENTAL

CPT- 11

Intervention Type: DRUG

65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery

Cisplatin

Intervention Type: DRUG

Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery

Celecoxib

Intervention Type: DRUG

400 mg, orally, twice per day beginning on day minus 3 and continue until the end of chemoradiation with CPT-11 and Cisplatin

Radiation

Intervention Type: RADIATION

4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks

Surgery

Intervention Type: PROCEDURE

Surgery will occur prior to chemoradiation therapy for those patients with resectable disease

Interventions

CPT- 11

65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery

Intervention Type: DRUG

Cisplatin

Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery

Intervention Type: 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

Intervention Type: DRUG

Radiation

4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks

Intervention Type: RADIATION

Surgery

Surgery will occur prior to chemoradiation therapy for those patients with resectable disease

Intervention Type: PROCEDURE

Other Intervention Names

Irinotecan; Cis-diammine-dichloro-platinum

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bert H. O'Neil, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Other Identifiers

CDR0000561610

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0203

Identifier Type: -

Identifier Source: org_study_id

NCT00280124

Identifier Type: -

Identifier Source: nct_alias