Combination Chemotherapy and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Esophageal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, carboplatin, and capecitabine, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Capecitabine may also make tumor cells more sensitive to radiation therapy. Giving combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with carboplatin and capecitabine followed by chemoradiotherapy in treating patients who are undergoing surgery for locally advanced esophageal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and dose-limiting toxicity of docetaxel when administered with carboplatin and capecitabine as neoadjuvant induction therapy in patients with locally advanced esophageal cancer. Secondary Determine the qualitative and quantitative toxic effects of this regimen in these patients. Determine the clinical and pathological response in these patients treated with neoadjuvant induction therapy comprising docetaxel, carboplatin, and capecitabine followed by chemoradiotherapy with capecitabine. OUTLINE: This is an open-label, dose-escalation study of docetaxel. Induction therapy: Patients receive docetaxel IV and carboplatin IV over 30-60 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 2 courses. Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Approximately 7 days after completion of induction therapy, patients proceed to chemoradiotherapy. Chemoradiotherapy: Patients receive oral capecitabine twice daily on days 1-42 and undergo radiotherapy once daily, 5 days a week, on days 1-40. Surgery: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter. PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.

Official Title
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Phase I Trial With Weekly Docetaxel, Capecitabine and Carboplatin as Induction Chemotherapy Followed by Concomitant Capecitabine and Radiotherapy in Patients With Locally Advanced Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: carboplatin
* Drug: docetaxel
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed esophageal or gastroesophageal junction cancer Locally advanced disease, meeting 1 of the following staging criteria: T3, N0, M0 disease Any T, N1, M0 disease Measurable or evaluable disease PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL Hepatic Bilirubin normal Meets 1 of the following criteria: Alkaline phosphatase (AP) normal AND AST/ALT ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST/ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST/ALT normal Renal Creatinine ≤ 2.0 mg/dL Creatinine clearance ≥ 80 mL/min Cardiovascular No uncontrolled congestive heart failure No symptomatic coronary artery disease No uncontrolled arrhythmias No myocardial infarction within the past 12 months No other uncontrolled clinically significant cardiac disease Gastrointestinal Able to swallow tablets Intact upper gastrointestinal tract No malabsorption syndrome Immunologic No history of unanticipated severe reaction to fluoropyrimidine No known hypersensitivity to fluorouracil No severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 No serious infection that requires continuous antibiotic therapy Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment No other prior or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No history of seizures No history of serious psychiatric illness that would preclude study compliance or giving informed consent No peripheral neuropathy > grade 1 PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy Radiotherapy No prior radiotherapy Other More than 28 days since prior investigational drugs No concurrent warfarin for active anticoagulation

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Drug: carboplatin|nan|
|Drug: docetaxel|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II esophageal cancer, stage III esophageal cancer