Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma involving the gastroesophageal junction or gastric cardia
• Central pathology review to determine evaluability of archived esophagogastroduodenoscopy (EGD)/biopsy sample
• NOTE: If archived sample was collected > 8 weeks prior to pre-registration (reg), is not available in a timely manner, or was collected outside of Mayo Clinic and considered unevaluable, then baseline EGD with primary tumor biopsy at Mayo Clinic must be performed unless clinically contraindicated; patient is allowed to enroll regardless of whether this Mayo Clinic tissue sample is evaluable; (Only 1 EGD with primary tumor biopsy performed at Mayo Clinic = 60% of predicted
• Adequate organ function = 60 mL/min/1.73 m^2 for patients with creatinine levels above or below the institutional normal
• Hemoglobin (Hgb) >= 9 g/dl without transfusion or epoetin dependency (= = 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Albumin >= 2.5 g/dl
• Female patients of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• NOTE: Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Female patients of childbearing potential must have a negative urine or serum pregnancy test = 1.5 cm in greatest dimension)
• T1N0M0, T4Nany, or in situ carcinoma
• Tumor must not extend 5 or more cm into the stomach
• Received prior treatment or receiving current treatment for this malignancy
• Prior radiation to chest or abdomen, or to > 30% of the marrow cavity
• Inadequate caloric or fluid intake whereby there is a current or likely future need for enteral or parenteral feeding during chemoradiation or the preoperative period
• Major surgery = = 35 mg/m^2 =< 56 days prior to registration
• Pre-existing motor or sensory neurotoxicity greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1
• Acute bacterial, viral, or fungal infection requiring treatment at the time of registration
• Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment
• Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations, or other co-morbid systemic illnesses or severe concurrent diseases which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Prior malignancy =< 5 years prior to registration (except non-melanotic skin cancer or carcinoma-in-situ of the cervix) (must be disease free for a minimum of 5 years); if there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for cancer
• Dementia or altered mental status that would prohibit the understanding and giving of informed consent
• Any of the following because this study involves an agent where the genotoxic, mutagenic and teratogenic effects are unknown:
• Pregnant or breastfeeding
• Patient of childbearing potential who is unwilling to employ adequate contraception
• Received live vaccine =< 30 days prior to registration