Capecitabine and Radiation Therapy with or without Pembrolizumab in Treating Participants with Resectable or Borderline Resectable Pancreatic Cancer

Inclusion Criteria

• The clinical, radiographic and pathologic evidence support a diagnosis of pancreatic adenocarcinoma, with histology confirmatory or suspicious for adenocarcinoma
• Must be determined to meet the criteria for resectable or borderline resectable pancreatic cancer based on the M.D. Anderson Cancer Center (MDACC) and Alliance Intergroup Criteria classification
• Be willing and able to provide written informed consent/assent for the trial
• Be >= 18 years of age on day of signing informed consent
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have completed 4-8 cycles of fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) prior to randomization and > 2 weeks but < 4 weeks prior to cycle 1 day 1 of treatment
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500 /mcL
• Platelets >= 100,000 / mcL
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
• Serum creatinine =< 1.5 X upper limit of normal (institutional upper limit of normal, IULN) or measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Serum total bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X IULN
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X IULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X IULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• In subjects requiring biliary decompression, metal stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed; subjects having plastic stent placement are not eligible
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should 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; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of trial treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has a plastic biliary stent for decompression
• Has metastatic disease as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• Has had prior surgery, chemotherapy (other than 4-8 cycles of FOLFIRINOX), targeted small molecule therapy, or radiation therapy for pancreatic cancer or prior treatment with radiation for other diagnoses to the expected pancreatic cancer treatment fields * Note: If subject received major surgery for reason other than pancreatic cancer, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); in patients without a known history of hepatitis B or C, serologies should be obtained at screening
• Has received a live vaccine within 30 days prior to the first dose of trial treatment
• Subjects who are unable or unwilling to discontinue use of prohibited medications
• Subject is unable or unwilling to participate a study related procedure
• Subject is a prisoner
• Significant history of uncontrolled cardiac disease defined as uncontrolled hypertension; unstable angina; myocardial infarction within the last 4 months; or uncontrolled congestive heart failure
• A serious uncontrolled medical disorder that in the opinion of the investigator would impair the ability of the subject to receive protocol therapy