Adaptive Radiation Therapy for the Treatment of Locally Advanced Unresectable Pancreatic Cancer

Inclusion Criteria

• Patients must have histologically or cytologically-confirmed pancreatic ductal adenocarcinoma (PDA)
• Patients must have locally advanced unresectable PDA * This includes the following- per National Comprehensive Cancer Network (NCCN) criteria: ** Unreconstructible involvement with the superior mesenteric vein or portal vein due to tumor or bland thrombus OR ** Solid tumor contact with greater than 180 degrees of the superior mesenteric artery or celiac artery OR ** Solid tumor contact with the aorta OR ** Patients with non-metastatic disease that is inoperable by virtue of the operation posing excessive risk to the patient * All patients must have been reviewed in the multidisciplinary conference and determined to have unresectable disease by a pancreatic surgeon and to have received or be ineligible for induction chemotherapy based on medical oncology assessment. Documentation of this review in EPIC meeting minutes will satisfy this requirement
• Patients enrolled onto the dose escalation arm may have started chemotherapy prior to initiation of radiation therapy and the last dose of chemotherapy must occur at least 2 weeks before start of ART
• Eastern Cooperative Oncology Group, or ECOG, performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1,500/µl
• Platelets (PLT) ≥ 100,000/µl
• Bilirubin less than 1.5 upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 X ULN
• Serum creatinine < 1.5 X ULN
• Women of childbearing potential must not be pregnant (negative pregnancy test within 72 hours prior to registration). Postmenopausal woman must have been amenorrheal and non-lactating for at least 12 months to be considered of non-childbearing potential. Men and women of childbearing potential must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for at least 6 months after therapy is completed
• Age ≥ 18 years
• Participants must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment, tissue sample collections, and follow-up

Exclusion Criteria

• Radiologically or cytologically confirmed metastatic disease
• Patients who have had any prior radiation therapy for pancreatic cancer
• Patients who have had prior chemoradiation to an overlapping volume
• Patients with adenosquamous carcinoma of the pancreas
• Subjects who have had chemotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier to < grade 2. Patients who received previous immunotherapy or other antibody therapy, within 28 days (immune related toxicities must have resolved to ≤ grade 2 prior to starting treatment). Study treatment may be started within these washout periods or with continuing toxicities if considered by the sponsor-investigator to be safe and within the best interest of the patient
• Concurrent non-study chemotherapy or biologic therapy
• A history of ataxia telangiectasia or other documented history of radiation hypersensitivity * Includes both bi- and mono-allelic likely pathogenic or pathogenic ATM mutations (variant of unknown significance [VUS] is acceptable)
• Serious, active infections requiring treatment with intravenous (IV) antibiotics