Preoperative Capecitabine, Oxaliplatin, Cetuximab, and Radiation Therapy for Locally Advanced Esophageal Adenocarcinoma

Not Applicable

Terminated

Brief Summary: The primary objective of this pilot study is to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection \[and then followed by post operative adjuvant capecitabine, oxaliplatin and cetuximab\] is feasible and tolerable.

Detailed Description: It is clear that new approaches are needed to improve the therapeutic ratio in esophageal cancer. This study proposes to evaluate the novel combination of preoperative capecitabine, oxaliplatin, and cetuximab concurrently with radiation therapy. This will be followed by esophagectomy 6-9 weeks after the completion of chemoradiation. Followed by further adjuvant chemotherapy. It is hypothesized that our novel combination of neoadjuvant capecitabine, oxaliplatin, and cetuximab combined with thoracoabdominal radiation therapy will be feasible and result in acceptable toxicity.

Recruitment & Eligibility

Inclusion Criteria

signed informed consent
patients 18 years of age or older
biopsy proven, non-recurrent primary adenocarcinoma of the thoracic esophagus or gastro-esophageal junction, disease confined to esophagus and peri-esophageal soft tissue, tumors at the gastroesophageal junction must be limited to no greater than 2 cm into the gastric cardia
clinical stage T3, N0-1 or T1-2, N1 and M0 or M1a (celiac axis lymph nodes are allowed)
Karnofsky Performance Status of >60%
forced expiratory volume at one second (FeV1) must be >1.0 L
adequate bone marrow reserve equal to or absolute neutrophil count (ANC) > 1500/mcl, total white blood cell count (WBC) > 3000/mcl, platelets >100,000/mcl and hemoglobin > 10.0 g/dl (transfusion permitted)
adequate hepatic function of direct serum bilirubin < 2 times the upper limit of normal, total bilirubin < 1.5 times the upper limit normal, alanine transaminase (ALT), aspartate transaminase (AST) < 2.5 times the upper limit normal, Alkaline phosphatase < 2.5 times the upper limit normal
creatinine clearance > 50 ml/min
female patients of childbearing potential must have a negative serum or urin pregnancy test within 7 days prior to starting therapy

Exclusion Criteria

no previous resection or attempted resection of an esophageal cancer
women who are pregnant or lactating
life expectancy < 3 months
serious, uncontrolled concurrent infection(s)
prior fluoropyrimidine therapy
prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known Dihydro Pyrimidine Dehydrogenase Deficiency (DPD) deficiency
treatment for other carcinomas within 5 years, except cured non-melanoma skin and treated in-situ cervical cancer
history of or evidence of uncontrolled diabetes
surgical procedure within 6 months of study entry
participation in any investigational drug study within 4 weeks preceding the start of study treatment
prior therapy with andy agent that specifically targets the Epidermal Growth Factor Receptor (EGFR) pathway
prior severe infusion reaction to a monoclonal antibody
acute hepatitis or known HIV
clinically significant cardia disease
evidence of metastases
other serious uncontrolled medical conditions that the investigator feels might compromise study participation
major surgery within 4 weeks of the start of treatment without complete recovery
lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
known, existing uncontrolled coagulopathy
unwillingness to give written informed consent
unwillingness to participate or inability to comply with the protocol for the duration of the study
neuropathy of grade 2 or greater

Arm && Interventions

Group	Intervention	Description
Capecitabine, oxaliplatin, cetuximab, and radiation therapy	Oxaliplatin	Patients enrolled on the trial will receive neoadjuvant combined capecitabine, oxaliplatin, cetuximab, and radiation therapy. This will be followed by surgical resection and adjuvant capecitabine, oxaliplatin, and cetuximab
Capecitabine, oxaliplatin, cetuximab, and radiation therapy	Capecitabine	Patients enrolled on the trial will receive neoadjuvant combined capecitabine, oxaliplatin, cetuximab, and radiation therapy. This will be followed by surgical resection and adjuvant capecitabine, oxaliplatin, and cetuximab
Capecitabine, oxaliplatin, cetuximab, and radiation therapy	Cetuximab	Patients enrolled on the trial will receive neoadjuvant combined capecitabine, oxaliplatin, cetuximab, and radiation therapy. This will be followed by surgical resection and adjuvant capecitabine, oxaliplatin, and cetuximab

Primary Outcome Measures

Name	Time	Method
Overall Toxicity	Up to 4 weeks	The primary objective of this pilot study was to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection and then followed by post operative adjuvant capecitabine, oxaliplatin and cetuximab is feasible with acceptable toxicity profile.

Secondary Outcome Measures