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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00448760
First received: March 15, 2007
Last updated: July 25, 2014
Last verified: August 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Pathologic Complete Response [ Time Frame: 8 - 16 weeks ] [ Designated as safety issue: No ]
    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:
  • Clinical Response [ Time Frame: 8 - 16 weeks ] [ Designated as safety issue: No ]

    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.


  • Median Progression-free Survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: October 2004
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00448760

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

Additional Information:
Publications:
Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00448760     History of Changes
Other Study ID Numbers: UMIAMI-20040006, SCCC-2003151, WIRB-20051464
Study First Received: March 15, 2007
Results First Received: January 16, 2013
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
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
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014