Celecoxib, Paclitaxel, and Carboplatin in Treating Patients With Cancer of the Esophagus

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. Celecoxib may also stop the growth of tumor cells by stopping blood flow to the tumor and/or may block the enzymes necessary for their growth. Combining celecoxib with paclitaxel and carboplatin before surgery may shrink the tumor so that it can be removed during surgery. Giving celecoxib alone after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving celecoxib together with paclitaxel and carboplatin works in treating patients who are undergoing surgery for esophageal cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the rate of complete pathological response and/or minimal residual microscopic disease in patients with squamous cell or adenocarcinoma of the esophagus treated with preoperative celecoxib, paclitaxel, and carboplatin. Secondary Determine the clinical response rate of patients treated with this regimen. Determine the chemotherapy-related toxicity of this regimen in these patients. Determine the time to progression, disease-free survival, and overall survival of patients treated with this regimen. OUTLINE: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning 3-7 days before the first dose of chemotherapy and continuing until the morning of planned surgical resection (between days 64 and 71). Approximately 28-56 days after resection, patients may resume oral celecoxib twice daily and continue for 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed periodically for 18 months after surgery. PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 18 months.

Official Title
-----------------
A Phase II Study Of Preoperative Celecoxib/Paclitaxel/Carboplatin For Squamous Cell And Adenocarcinoma Of The Esophagus

Conditions
-----------------
Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: celecoxib
* Drug: paclitaxel
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed esophageal cancer of 1 of the following cellular types: Squamous cell Adenocarcinoma Potentially resectable disease No distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 80-100% Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 No bleeding disorder Hepatic Bilirubin normal AST and ALT less than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal Creatinine no greater than 2.0 mg/dL Cardiovascular No significant history of unstable cardiovascular disease No inadequately controlled hypertension No angina No myocardial infarction within the past 6 months No ventricular cardiac arrhythmias requiring medication No congestive heart failure that would preclude study therapy Pulmonary Pulmonary function acceptable for surgery No interstitial pneumonia No interstitial fibrosis Gastrointestinal No history of peptic ulcer disease No irritable bowel syndrome No inflammatory bowel disease No chronic diarrhea No bowel obstruction within the past 5 years Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates No hypersensitivity to paclitaxel or carboplatin No other serious underlying medical condition that would preclude study therapy No significant psychiatric illness that would preclude study compliance No uncontrolled diabetes mellitus No uncontrolled infection HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No concurrent chronic steroid use except inhaled mometasone or fluticasone Radiotherapy Not specified Surgery Not specified Other More than 3 weeks since other prior clinical trial therapy At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs) No concurrent chronic NSAID use (7 or more days of continuous therapy per month OR 3 or more days of therapy per week) No other concurrent investigational agents No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital) No other concurrent cyclo-oxygenase (COX)-2 inhibitors No concurrent lithium or fluconazole Concurrent low-dose aspirin (325 mg/day or less) allowed for cardiovascular prophylaxis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|Dosed to an AUC of 6 by the Calvert formula, intravenously over 1 hour after paclitaxel on days 1, 22, and 43.|
|Drug: celecoxib|400 mg orally BID begins 3-7 days before the first dose of chemotherapy to the morning of surgery. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year total, that is, 1 year from the date of surgery + 2 weeks unless tumor recurrence is documented.|
|Drug: paclitaxel|200 mg/m2 as a 3-hour intravenous infusion on days 1, 22, and 43.|
|Procedure: adjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year.|
|Procedure: conventional surgery|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|
|Procedure: neoadjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate at time of surgical resection |  | At completion of pathology report. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate |  | At the time of tumor assessment obtained prior to definitive surgery approximately 1-2 weeks prior to surgical resection. | 
| Disease-free survival |  | From start of treatment to time of recurrent disease measured postoperatively every 6 months for 18 months. | 
| Overall survival |  | 18 months after surgery | 
| Toxicities and safety |  | 30 days after completion of study treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer (lymph node metastasis only)