Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer

Inclusion Criteria:

• At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX or NALIRIFOX or gemcitabine/nab-paclitaxel. Patients are permitted to receive more than 1 type of chemotherapy for toxicity reasons, but not for disease progression. "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle

• BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:

• Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma

• Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network [NCCN] guidelines and institutional tumor board review)

• Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, CT chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment

• Age ≥ 18 years

• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2

• Required initial laboratory values:

All laboratory values must be obtained any time prior to initiation of chemotherapy up to 30 days post initiation of chemotherapy

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)

• BASELINE CA19-9 AND BILIRUBIN REQUIREMENTS: The purpose is to obtain a baseline CA19-9 in the setting of a normal (or close to normal) bilirubin, since serologic response by serial CA19-9 measurements is part of post-chemotherapy eligibility criteria

• If baseline CA19-9 > 37 U/mL the concurrent bilirubin must be ≤ 1.5 x ULN. (Note: if the bilirubin is not ≤ 1.5 x ULN both the CA19-9 and concurrent bilirubin can be repeated until bilirubin is ≤ 1.5 x ULN, as long as done within specified timeframe [up to 30 days post chemotherapy initiation])

• If baseline CA19-9 U/mL ≤ 37, there are no restrictions on the required concurrent bilirubin level, and this can be the accepted baseline value

• Prior radiation treatment

• Has the patient had prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Prior non-overlapping radiation (e.g., breast, head and neck, extremity) is permitted

• If uncertain about prior overlap, please contact the study principal investigator, Dr. Nina Sanford

• POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:

• If baseline CA19-9 is elevated (defined as > 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL

• If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL

• No active duodenal or gastric ulcers

• No direct tumor invasion of the bowel or stomach

• Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment, with restaging CT showing at least stable disease

• Not pregnant and not nursing

• No cardiac condition that was the primary reason for hospitalization in the last 6 months

• New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial