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

December 14, 2016 updated by: University of Miami

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant + Adjuvant Chemotherapy
Drug: Docetaxel
Intravenously, 25 mg/m2, over 30 minutes, 2 cycles
Other Names:
  • Taxotere
Drug: Floxuridine
Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
8 - 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 24 months
24 months
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.
8 - 16 weeks
Median Progression-free Survival (PFS)
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

March 15, 2007

First Submitted That Met QC Criteria

March 15, 2007

First Posted (Estimate)

March 19, 2007

Study Record Updates

Last Update Posted (Estimate)

February 7, 2017

Last Update Submitted That Met QC Criteria

December 14, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20040006
  • SCCC-2003151 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)
  • WIRB-20051464 (Other Identifier: Western Institutional Review Board)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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