Clinical Trials

PRIMARY OBJECTIVES:

     l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with HER2-overexpressing esophageal adenocarcinoma.

     SECONDARY OBJECTIVES:

     I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma.

     II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma.

     III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab.

     IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation.

     V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma.

     TERTIARY OBJECTIVES:

     I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score.

     II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response.

     III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation.

     IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E.

     V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival.

     OUTLINE: This is a multicenter study. Patients are stratified according to presence of adenopathy (yes vs no), and involved celiac nodes (absent vs presence ≤ 2 cm). Patients are randomized to 1 of 2 treatment arms.

     ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 and trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.

     ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36.

     Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.

     Patients may undergo blood and tumor tissue samples collection (during surgery) for correlative studies and tissue bank. Patients may complete the Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) and the EuroQol (EQ-5D) questionnaires at baseline and periodically during study.

     After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.