Conformal Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer that has Spread to the Liver

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas metastatic to the liver (liver metastases confirmed pathologically or radiographic liver lesions most consistent with metastases in a patient with pathologically proven pancreatic adenocarcinoma)
• Germline or biallelic somatic pathogenic mutations in the core HR genes including BRCA1, BRCA2, PALB2 and ATM genes are required for dose escalating cohort. Pathogenic germline or biallelic somatic alterations other HR genes including (BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, RTEL1) are allowed in the expansion cohort. Confirmation of the required mutations can be from Memorial Sloan Kettering (MSK) Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) or any other approved germline genetic testing for eligibility purposes
• >= 1 liver lesion(s) measurable on a contrast-enhanced liver computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT performed within 6 weeks prior to study entry. Any tumor location within the liver is allowed
• At least 1 liver metastasis measuring =< 7 cm
• Extrahepatic disease outside the liver is permitted if the hepatic disease is judged to be life-limiting (1-2 sites of disease are allowed, including lung and non-regional nodes, up to and including 5 individual lesions)
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Any prior chemotherapy therapy is allowed including prior treatment with platinum containing chemotherapy and irrespective of response to prior therapy
• Prior treatment with Food and Drug Administration (FDA)-approved or investigational biologics or novel molecularly targeted therapies, including oral or IV formulations, are permitted. Patients must be off prior targeted therapy for at least 14 days or 4 half-lives prior to the initiation of the study treatment
• Use of an effective means of contraception in men and women of child-bearing potential
• Absolute neutrophil count (ANC) > 1000/mm^3 (within 14 days prior to study entry)
• Hemoglobin > 9 gm/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] > 9.0 g/dl is acceptable) (within 14 days prior to study entry)
• Platelets > 100,000/mm^3 (within 14 days prior to study entry)
• Serum creatinine < 1.5 mg/dl overall rate (OR) creatinine clearance of > 50 cc/min
• Total bilirubin < 1.8 mg/dL (within 14 days prior to study entry)
• Prothrombin time/international normalized ratio (INR) < 1.7 (within 14 days prior to study entry)
• Albumin >= 28 g/L (within 14 days prior to study entry)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times upper limit of normal (ULN) (within 14 days prior to study entry)
• Alkaline phosphatase (ALP) < 2.5 times ULN (within 14 days prior to study entry)

Exclusion Criteria

• Prior invasive malignancy, except non-melanoma skin cancer, unless disease free for a minimum of 3 years
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• History of underlying liver disease, including but not limited to cirrhosis, hepatitis or hemochromatosis
• History of major liver resection
• Variants of unknown significance (VUS) in core or non-core HR genes will be excluded
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Clinical ascites
• Single right kidney. (A single left kidney is allowed)
• Pregnancy, nursing women, or women of childbearing potential, and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic