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

Phase 2

Completed

• Conditions: Esophageal Cancer
• Interventions: Drug: Docetaxel; Drug: Floxuridine; Drug: Leucovorin; Drug: Oxaliplatin; Genetic: Microarray analysis; Genetic: reverse transcriptase-polymerase chain reaction; Procedure: Conventional surgery

• Registration Number: NCT00448760
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2004-10
• Study First Submitted: 2007-03-15
• Study First Submitted QC: 2007-03-15
• Study First Posted: 2007-03-19
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Results First Submitted: 2013-01-16
• Results First Submitted QC: 2013-01-16
• Results First Posted: 2013-02-18
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-14
• Last Update Posted: 2017-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant + Adjuvant Chemotherapy	reverse transcriptase-polymerase chain reaction	-
Neoadjuvant + Adjuvant Chemotherapy	Conventional surgery	-
Neoadjuvant + Adjuvant Chemotherapy	Microarray analysis	-
Neoadjuvant + Adjuvant Chemotherapy	Oxaliplatin	-
Neoadjuvant + Adjuvant Chemotherapy	Docetaxel	-
Neoadjuvant + Adjuvant Chemotherapy	Floxuridine	-
Neoadjuvant + Adjuvant Chemotherapy	Leucovorin	-

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response	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

Name	Time	Method
Overall Survival	24 months
Clinical Response	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.
Median Progression-free Survival (PFS)	24 months

Trial Locations

Locations (1)

University of Miami Sylvester Comprehensive Cancer Center - Miami; 🇺🇸 Miami, Florida, United States