Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma

Inclusion Criteria: * Histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction. * HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy. * Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen. * T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible. * Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm. * If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach. * No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. * Age ≥ 18 and ≤ 75 years. * ECOG performance status 0 or 1. * Adequate hematological, renal and hepatic functions defined as: * neutrophiles ≥ 1.5 x 109/L * platelets ≥ 100 x 109/L * hemoglobin ≥ 5.6 mmol * total bilirubin ≤ 1.5 x upper normal limit * creatinine clearance (Cockroft) \> 60 ml/min * Adequate left ventricular ejection fraction defined as an LVEF of ≥55%. * Written, voluntary informed consent. * Patients must be accessible to follow up and management in the treatment center. Exclusion Criteria: * A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer. * Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment. * Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. * Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. * Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors. * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization. * Pulmonary fibrosis and/or severely impaired lung function. * Pre-existing motor or sensory neurotoxicity greater than WHO grade 1. * Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. * Dementia or altered mental status that would prohibit the understanding and giving of informed consent * Inadequate caloric- and/or fluid intake.