Phase I Dose Escalation of Stereotactic Radiosurgical Boost for Locally Advanced Esophageal Cancer

Study Overview
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Brief Summary
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To study the safety and feasibility of stereotactic radiation dose escalation following neoadjuvant chemotherapy with concurrent conventionally fractionated radiation, by evaluating the acute and late toxicity of treatment.

Detailed Description
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This study will evaluate the safety and feasibility of delivering radiation dose escalation using hypofractionated radiosurgery in locally advanced esophageal cancer. The dose escalation will be delivered using an image-guided radiosurgical boost to the tumor volume, following a neoadjuvant regimen consisting of oxaliplatin, capecitabine, and conventionally fractionated radiotherapy. In addition, we will evaluate the utility of PET-FDG before and after neoadjuvant chemoradiation in predicting the pathologic response to pre-operative treatment. We will study the effect of this regimen on pathologic complete response rates and complete resection rates at surgery among patients with locally advanced esophageal cancer and determine patterns of failure and rates of progression-free survival. Finally, we plan to characterize in an exploratory manner the correlation between molecular markers and pathologic findings following pre-operative chemoradiation.

Official Title
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Phase I Study of Dose Escalation Using Image-guided Radiotherapy to Deliver a Stereotactic Radiosurgical Boost After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer

Conditions
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Esophageal Neoplasms, Carcinoma, Squamous Cell, Adenocarcinoma, Esophageal Cancer

Intervention / Treatment
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* Drug: Capecitabine (Xeloda)
* Drug: [18-F] Fluorodeoxyglucose (FDG)
* Drug: 5-Fluorouracil (5-FU)
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- Confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus by pathologist. Endoscopic ultrasound or CT evidence of tumor penetration through the esophageal wall or involvement of regional lymph nodes, without evidence of distant metastasis No prior chest radiation therapy No prior chemotherapy for esophageal cancer Age greater than 18 years No infections requiring antibiotic treatment Able to care for self Patients must have acceptable liver, kidney and bone marrow function. The effects of the chemotherapy drugs on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use adequate contraception. Exclusion Criteria:- Patients receiving any other investigational agents Evidence of distant metastases Uncontrolled medical illness Any malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Pregnant and breastfeeding women are excluded. HIV-positive patients

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

| Intervention/Treatment |
| --- |
|Drug: Capecitabine (Xeloda)|PO bid daily on RT days: 500mg & 150mg tabs for dose 825mg/m2 bid AM/PM (total daily dose 1650mg/m2)|
|Drug: [18-F] Fluorodeoxyglucose (FDG)|5-10 mCi IV administration|
|Drug: 5-Fluorouracil (5-FU)|200mg/m2 continuous venous infusion|
|Drug: Carboplatin|AUC 2, based onCalvert formula IV infusion|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A complete assessment of all pathologic specimens (biopsy and definitive surgical) to document the histology, grade, depth of invasion, lymphovascular or perineural invasion. |  |  | 
| The inked margins on the definitive surgical specimen will be inked and margin status, size of the tumor, evidence of residual tumor will be recorded. |  |  | 
| Patients' responses to therapy will be evaluated clinically after completion of their neoadjuvant chemoradiation. |  | after completion of their neoadjuvant chemoradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical exam |  | Once every three months for two years, then every six months for three years and then once a year. | 
| CT scan |  | Three months after completion of therapy, then every six months for three years then once a year for until 5 years from completion of therapy. | 
| Upper endoscopy |  | Three months after completion of therapy, then every six months for three years then once a year for until 5 years from completion of therapy. | 
| Patterns of failure and the 2-year progression-free survival (PFS) rate. |  | 2 years |