Inclusion Criteria:

          -  Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of
             the esophagus or gastroesophageal junction (GEJ) within 90 days prior to registration

               -  Gastroesophageal junction tumors must be Siewert type I/II

          -  Required diagnostic workup for study entry:

               -  History/physical examination prior to registration

               -  Computed tomography (CT) of the chest/abdomen with intravenous contrast within 28
                  days prior to registration; If CT contrast is contraindicated magnetic resonance
                  imaging (MRI) of the chest/abdomen without contrast is permitted

               -  Endoscopic ultrasound (if technically feasible) within 90 days prior to
                  registration

               -  Whole body positron emission tomography (PET)/CT scan within 42 days prior to
                  registration: Note: scan will be used for radiation treatment planning, in
                  addition to ruling out metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days
             prior to registration

          -  White blood cell (WBC) ≥ 3,000/mcL (within 14 days prior to registration)

          -  Absolute neutrophil count ≥ 1,500/mcL (within 14 days prior to registration)

          -  Hemoglobin ≥ 9 gm/dL (within 14 days prior to registration)

          -  Platelets ≥ 100,000/mcL (within 14 days prior to registration)

          -  Creatinine clearance of ≥ 50 ml/min (as calculated by Cockcroft-Gault equation)
             (within 14 days prior to registration)

          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to
             registration)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 14
             days prior to registration)

          -  Patients must, in the opinion of a thoracic surgeon and/or multidisciplinary team, not
             be a candidate for surgery but are candidates for chemoradiation

          -  Patients must, in the opinion of a treating gastroenterologist, have a tumor that is
             amenable to intratumoral injection with at least 1 mL (1 x 10^12 vp/mL) of OBP-301 and
             be a candidate for 3 endoscopy procedures

          -  Female patients of child bearing potential must have a negative serum/urine pregnancy
             test within 14 days prior to study entry. A female not of childbearing potential is
             one who has undergone a hysterectomy, bilateral oophorectomy, tubal ligation, or who
             has had no menses for 12 consecutive months

          -  Patients of reproductive potential must agree to use effective contraception for the
             duration of study treatment as well as 6 months (for women) or 12 months (for men)
             after the last administered injection of OBP-301. Effective contraception includes
             oral contraceptives, implantable hormonal contraception, double-barrier method or
             intrauterine device

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to study entry

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  Known acute or chronic hepatitis B or C infection (testing not required prior to study
             entry in patients with no known history of hepatitis B or C)

               -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
                  viral load must be undetectable on suppressive therapy, if indicated

               -  For patients with a history of hepatitis C virus (HCV) infection, they must (i)
                  have been treated and cured, (ii) for patients with HCV infection who are
                  currently on treatment, they are eligible if they have an undetectable HCV viral
                  load

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months prior to study entry are eligible
             for this trial

        Exclusion Criteria:

          -  Definitive clinical or radiologic evidence of metastatic disease including:

               -  Positive malignant cytology of the pleura, pericardium or peritoneum

               -  Radiographic evidence of involvement of any adjacent mediastinal structure, e.g.
                  aorta, trachea, which would increase the risk of repeated endoscopic
                  interventions

               -  Radiographic evidence of distant organ involvement

               -  Non-regional lymph nodes that cannot be contained within a radiation field

          -  More than 1 esophageal lesion

          -  Prior systemic chemotherapy for the study cancer

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          -  Biopsy-proven tumor invasion of the tracheobronchial tree or presence of
             tracheoesophageal fistula or recurrent laryngeal or phrenic nerve paralysis

          -  For patients with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, a New York Heart Association functional
             classification 2C or worse

          -  Uncontrolled diabetes

          -  Infection requiring IV antibiotics at the time of registration

          -  Patients requiring immunosuppressive medications including chronic suppressive steroid
             therapy (greater than the equivalent of 20 mg/day of prednisone), methotrexate,
             azathioprine and TNF-alpha blockers within 7 days prior to study entry

          -  Received live vaccine within 30 days prior to registration

          -  Received a blood transfusion, hematopoietic agent; granulocyte-colony stimulating
             factor (G-CSF), and/or oxygen supplementation within 7 days before the screening lab

          -  Breast feeding females