radiation therapy, paclitaxel, and carboplatin with or without trastuzumab in treating patients with esophageal cancer

Conditions: Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Stage IB Esophageal Cancer AJCC v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7

Summary: this randomized phase iii trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. radiation therapy uses high-energy x-rays to kill tumor cells. drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. it is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

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 human epidermal growth factor receptor 2 (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. patient-reported quality of life 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: 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 trastuzumab intravenously (iv) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel iv over 60 minutes and carboplatin iv over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. 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 30-60 minutes on days 1, 8, 15, 22, 29, and 36. within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. after completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

Eligibility criteria:
inclusion criteria: * pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm * endoscopy with biopsy * prior to step 1 registration but within 56 days prior to step 2 registration * intent to submit tissue for central her2 testing * stage t1n1-2, t2-3n0-2, according to the american joint committee on cancer (ajcc) 7th edition staging, based on the following minimum diagnostic work-up: * chest/abdominal/pelvic computed tomography (ct) or whole-body positron emission tomography (pet)/ct (note: if ct is performed at this time point, whole-body pet/ct will be required prior to step 2 registration; pet/ct of skull base to mid-thigh is acceptable) (note: if adenopathy is noted on ct or whole-body pet/ct scan, an endoscopic ultrasound is not required prior to step 2 registration as long as adequate tissue has been obtained for central her2 testing) * patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =\< 2 cm * patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula * zubrod performance status 0-2 * absolute neutrophil count (anc) \>= 1,500 cells/mm\^3 * platelets \>= 100,000 cells/mm\^3 * hemoglobin \>= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin \[hgb\] \>= 8.0 g/dl is acceptable) * creatinine =\< 2 times upper limit of normal * bilirubin =\< 1.5 times upper limit of normal * aspartate aminotransferase (ast) =\< 3.0 times upper limit of normal * for women of childbearing potential, a negative serum or urine pregnancy test * patients must sign a study-specific informed consent prior to study entry * conditions for patient eligibility prior to step 2 registration (her2-positive patients only) * her2 expressing adenocarcinoma of the esophagus centrally * surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration * radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration * consultation with a medical oncologist within 56 days prior to step 2 registration * stage t1n1-2, t2-3n0-2, according to the ajcc 7th edition staging, based upon the following minimum diagnostic work-up: * history/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration * whole-body pet/ct scan within 56 days prior to step 2 registration (if only ct performed prior to step 1 registration) * endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per ct or whole-body pet/ct scan * electrocardiogram (ekg) within 56 days prior to step 2 registration * serum creatinine =\< 2 x the upper limit or normal within 14 days prior to step 2 registration * zubrod performance status 0-2 within 14 days prior to step 2 registration * for women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration * left ventricular ejection fraction (lvef) \>= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (muga) scan within 56 days prior to step 2 registration * women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab exclusion criteria: * patients with cervical esophageal carcinoma * patients with t1n0 disease, t4 disease, and proximal esophageal cancers (15-24 cm) * prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable * prior radiation therapy for esophageal cancer or prior chest radiotherapy * prior anthracycline or taxane * evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi * prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible) * medical contraindications to esophagectomy * prior therapy with any agent targeting the her2 pathway or human epidermal growth factor receptor 1 (her1) (epidermal growth factor receptor \[egfr\]) pathway * prior therapy with trastuzumab * prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody * previous history of congestive heart failure * severe, active comorbidity, defined as follows: * unstable angina in the last 6 months * transmural myocardial infarction within the last 6 months * acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * acquired immune deficiency syndrome (aids) based upon current centers for disease control and prevention (cdc) definition; note, however that human immunodeficiency virus (hiv) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients * pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception