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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00448760
Recruitment Status : Completed
First Posted : March 19, 2007
Results First Posted : February 18, 2013
Last Update Posted : February 7, 2017
Information provided by (Responsible Party):
University of Miami

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.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: Docetaxel Drug: Floxuridine Drug: Leucovorin Drug: Oxaliplatin Genetic: Microarray analysis Genetic: reverse transcriptase-polymerase chain reaction Procedure: Conventional surgery Phase 2

Detailed Description:



  • 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.


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2004
Actual Primary Completion Date : April 2010
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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

Primary Outcome Measures :
  1. Pathologic Complete Response [ Time Frame: 8 - 16 weeks ]
    No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy.

Secondary Outcome Measures :
  1. Clinical Response [ Time Frame: 8 - 16 weeks ]

    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.

  2. Median Progression-free Survival (PFS) [ Time Frame: 24 months ]
  3. Overall Survival [ Time Frame: 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • No prior chemotherapy or radiotherapy to the esophagus
  • No oral cryotherapy (e.g., ice chips) on day 1 of each course

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00448760

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Study Chair: Bach Ardalan, MD University of Miami Sylvester Comprehensive Cancer Center

Publications of Results:
Responsible Party: University of Miami Identifier: NCT00448760     History of Changes
Other Study ID Numbers: 20040006
SCCC-2003151 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
WIRB-20051464 ( Other Identifier: Western Institutional Review Board )
First Posted: March 19, 2007    Key Record Dates
Results First Posted: February 18, 2013
Last Update Posted: February 7, 2017
Last Verified: December 2016

Keywords provided by University of Miami:
stage II esophageal cancer
stage III esophageal cancer
adenocarcinoma of the esophagus

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic