Preoperative Therapy With Oxaliplatin/Docetaxel/Capecitabine and Radiation in Resectable Esophagus Cancer

Study Overview
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Brief Summary
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In this phase I/II trial, we will evaluate a novel combination of chemotherapy, used concurrently with radiation therapy, in the preoperative therapy of locoregional carcinoma of the esophagus and gastroesophageal junction. In the brief phase I portion of this trial, we will determine whether 2 drugs (docetaxel/oxaliplatin) or 3 drugs (docetaxel/oxaliplatin/capecitabine) can be used concurrently with radiation therapy. If the 3-drug regimen is tolerated, the phase II portion will proceed with this regimen. If the 3-drug combination is considered too toxic, the phase II study will proceed with docetaxel/oxaliplatin in combination with radiation therapy.

Detailed Description
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Upon determination of eligibility, patients will be receive: Oxaliplatin + Docetaxel + Capecitabine + Radiation therapy If the three-drug chemotherapy regimen, with radiation therapy, is tolerable, this regimen will be taken forward into the phase II portion of the trial. If the three-drug regimen is too toxic, the phase II portion will proceed with the two-drug regimen Oxaliplatin + Docetaxel + Radiation therapy

Official Title
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A Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction

Conditions
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Esophagus Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Docetaxel
* Drug: Capecitabine
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in this study, you must meet the following criteria: Adenocarcinoma or squamous cell carcinoma of the esophagus or G/E junction. Must be surgical candidates No previous treatment for esophageal cancer Must have measurable or evaluable disease Able to perform activities of daily living with minimal to no assistance Adequate bone marrow, liver and kidney function Provide written informed consent Exclusion Criteria: You cannot participate in this study if any of the following apply to you: Tumor location in the proximal esophagus Metastatic disease or locally advanced cancer Moderate to severe peripheral neuropathy Serious pre-existing medical illnesses Significant heart disease Treated for an invasive cancer within the previous 5 years Women who are pregnant or breast-feeding Age < 18 years Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Oxaliplatin 40 mg/m2 intravenously (IV) over 2 hours and docetaxel 20 mg/m2 IV over 30 minutes on days 1, 8, 15, 22, and 29. Radiation therapy began concurrently with day 1 of chemotherapy at a dose of 1.8 Gy/d Monday through Friday to a total of 45 Gy (25 fractions). Patients were to have esophageal resection after completion of preoperative therapy during weeks 9 to 12 and after all treatment-related side effects were resolved. | Drug: Oxaliplatin<br>* 40 mg/m2 IV over 2 hours on days 1, 8, 15, 22, and 29 in both treatment cohorts<br>* Other names: Eloxatin;Drug: Docetaxel<br>* 20 mg/m2 IV over 30 minutes was administered on days 1, 8, 15, 22, and 29 in both cohorts<br>* Other names: Taxotere;Radiation: Radiation therapy<br>* In both cohorts, radiation therapy began concurrently with day 1 of chemotherapy at a dose of 1.8 Gy/d Monday through Friday to a total of 45 Gy (25 fractions).<br>* Other names: RT;|
| Experimental: Cohort 2<br>Oxaliplatin 40 mg/m2 intravenously (IV) over 2 hours and docetaxel 20 mg/m2 IV over 30 minutes on days 1, 8, 15, 22, and 29. Capecitabine was administered 1000 mg/m2 orally twice daily on days 1 to 7, 15 to 21, and 29 to 35. Radiation therapy began concurrently with day 1 of chemotherapy at a dose of 1.8 Gy/d Monday through Friday to a total of 45 Gy (25 fractions). Patients were to have esophageal resection after completion of preoperative therapy during weeks 9 to 12 and after all treatment-related side effects were resolved. | Drug: Oxaliplatin<br>* 40 mg/m2 IV over 2 hours on days 1, 8, 15, 22, and 29 in both treatment cohorts<br>* Other names: Eloxatin;Drug: Docetaxel<br>* 20 mg/m2 IV over 30 minutes was administered on days 1, 8, 15, 22, and 29 in both cohorts<br>* Other names: Taxotere;Drug: Capecitabine<br>* In Cohort 2, capecitabine was administered 1000 mg/m2 orally twice daily on days 1 to 7, 15 to 21, and 29 to 35.<br>* Other names: Xeloda;Radiation: Radiation therapy<br>* In both cohorts, radiation therapy began concurrently with day 1 of chemotherapy at a dose of 1.8 Gy/d Monday through Friday to a total of 45 Gy (25 fractions).<br>* Other names: RT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response Rate (PCRR), the Percentage of Patients Who Have No Evidence of Cancer in Their Surgical Specimen Following Surgery | The absence of any residual tumor cells in a histologic evaluation of a tumor specimen following surgery is defined as a complete pathologic response | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival (DFS) | Defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death from any cause. | 18 months | 
| Overall Survival (OS) | Length of time, in months, that patients were alive from their first date of protocol treatment until death. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagus Cancer