Combination Chemotherapy in Treating Patients With Previously Untreated Stage II or Stage III Esophageal Cancer That Can Be Removed By Surgery
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Docetaxel; Floxuridine; Leucovorin; Oxaliplatin; Microarray analysis; reverse transcriptase-polymerase chain reaction; Conventional surgery
Intervention type(s): Drug; Drug; Drug; Drug; Genetic; Genetic; Procedure
Intervention description(s): Intravenously, 25 mg/m2, over 30 minutes, 2 cycles; Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles; Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles; Intravenously, 85 mg/m2, over 2 hours, 2 cycles; Analysis of tumor for pathologic response to protocol therapy; Analysis of tumor for pathologic response to protocol therapy; Surgical removal of tumor for correlative studies
Other intervention name(s): Taxotere; FUdR
Intervention MeSH terms: Leucovorin; Docetaxel; Oxaliplatin; Floxuridine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the esophagus