Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinomaor squamous cell carcinoma (SCC) 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 magneticresonance imaging (MRI) of the chest/abdomen without contrast is permitted

• Bronchoscopy for squamous cell carcinoma (SCC) tumors that are adjacent to theairway to exclude a tracheoesophageal fistula within 42 days prior toregistration

• Endoscopic ultrasound (if technically feasible) within 90 days prior toregistration

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

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 daysprior 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 toregistration)

• 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 isamenable to intratumoral injection with at least 1 mL (1 x 10^12 vp/mL) of OBP-301and be a candidate for 3 endoscopy procedures

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

• Patients of reproductive potential must agree to use effective contraception for theduration 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 includesoral contraceptives, implantable hormonal contraception, double-barrier method orintrauterine device

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

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

• For patients with evidence of chronic hepatitis B virus (HBV) infection, theHBV 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 arecurrently on treatment, they are eligible if they have an undetectable HCVviral load

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months prior to study entry areeligible 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 endoscopicinterventions

• Tracheoesophageal fistula

• 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 ofradiation therapy fields

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

• For patients with known history or current symptoms of cardiac disease, or historyof treatment with cardiotoxic agents, a New York Heart Association functionalclassification 2C or worse

• Uncontrolled diabetes

• Infection requiring IV antibiotics at the time of registration

• Patients requiring immunosuppressive medications including chronic suppressivesteroid 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 stimulatingfactor (G-CSF), and/or oxygen supplementation within 7 days before the screening lab

• Breast feeding females