Combination Chemotherapy in Treating Patients With Previously Untreated Stage II or Stage III Esophageal Cancer That Can Be Removed By Surgery

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, floxuridine, docetaxel, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with previously untreated stage II or stage III esophageal cancer that can be removed by surgery.

Detailed Description
-----------------
OBJECTIVES: Primary Determine whether neoadjuvant chemotherapy comprising oxaliplatin, floxuridine, docetaxel, and leucovorin calcium improves the rate of pathologic complete response in patients with previously untreated, resectable stage II or III adenocarcinoma of the esophagus. Secondary Determine the progression-free and overall survival of patients treated with this regimen. Determine the clinical response rates (complete response and partial response) in patients treated with this regimen. Evaluate thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and mRNA sequence, to determine the altered spots as related to drug resistance in these patients. Evaluate the potential for genome-wide gene expression profiling to predict response to therapy, recurrence, progression-free survival, overall survival, and drug sensitivity and resistance in these patients. Define the role of 5' untranslated region (5'-UTR) on translation and drug resistance in these patients. Evaluate, by bone marrow aspirate analysis and flow cytometry, the initial presence of cancer cells in the marrow, and clearance of these cells after treatment with this regimen. Evaluate the safety of this regimen in these patients. Assess quality of life of patients during and after treatment with this regimen. OUTLINE: This is a nonrandomized, open-label study. Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and docetaxel IV over 30 minutes, floxuridine IV over 24 hours, and leucovorin calcium IV over 24 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after completion of chemotherapy. Patients who achieve pathologic complete response (pCR) receive no further chemotherapy. Patients who have not achieved a pCR receive 2 courses of adjuvant chemotherapy (same regimen as the neoadjuvant chemotherapy) beginning 3 weeks after surgery. Patients undergo blood and tissue collection periodically for correlative studies. Samples are analyzed for thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and mRNA sequence by bone marrow aspirate, flow cytometry, and quantitative reverse transcriptase-polymerase chain reaction. Quality of life will be assessed at baseline, after neoadjuvant chemotherapy, after adjuvant therapy, and at the first 3-month follow-up visit. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Official Title
-----------------
A Nonrandomized Phase II Study: Feasibility and Outcome of Neo Adjuvant Chemotherapy With Oxaliplatin, Fluorodeoxyuridine (FUdR), Taxotere and Leucovorin in the Treatment of Previously Untreated Advanced Esophago-Gastric Carcinoma

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

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: Floxuridine
* Drug: Leucovorin
* Drug: Oxaliplatin
* Genetic: Microarray analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Procedure: Conventional surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of adenocarcinoma of the esophagus meeting the following criteria: Stage II or III disease Resectable disease Previously untreated disease No stage I (mucosal only) or stage IV (metastatic) disease PATIENT CHARACTERISTICS: WBC > 3,000/mm^3 Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Creatinine ≤ 2.0 mg/dL Bilirubin < 2 times normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must have central venous access No other malignancy within the past 5 years No concurrent medical or psychiatric problem that would preclude study treatment No contraindications to paclitaxel PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy to the esophagus No oral cryotherapy (e.g., ice chips) on day 1 of each course

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant + Adjuvant Chemotherapy<br> | Drug: Docetaxel<br>* Intravenously, 25 mg/m2, over 30 minutes, 2 cycles<br>* Other names: Taxotere;Drug: Floxuridine<br>* Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles<br>* Other names: FUdR;Drug: Leucovorin<br>* Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles<br>Drug: Oxaliplatin<br>* Intravenously, 85 mg/m2, over 2 hours, 2 cycles<br>Genetic: Microarray analysis<br>* Analysis of tumor for pathologic response to protocol therapy<br>Genetic: reverse transcriptase-polymerase chain reaction<br>* Analysis of tumor for pathologic response to protocol therapy<br>Procedure: Conventional surgery<br>* Surgical removal of tumor for correlative studies<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response | No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy. | 8 - 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response | Overall response = Complete response (CR) + Partial Response (PR). Evaluated via endoscopic ultrasounds, PET and CT scans of the chest: Complete Response (CR) applies to participants complete disappearance of all measurable and evaluable disease. No new lesion. No disease related symptoms. No evidence of non-evaluable disease, including tumor markers and other laboratory values. Partial Response (PR) applies to participants with at least 50 percent reduction in the sum of the products of bi-dimensional perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. | 8 - 16 weeks | 
| Median Progression-free Survival (PFS) |  | 24 months | 
| Overall Survival |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II esophageal cancer, stage III esophageal cancer, adenocarcinoma of the esophagus