HYPERION CCA: a Phase 2 Trial of Systemic Therapy With or Without Liver-directed Radiation Therapy for Patients With Advanced Intrahepatic Cholangiocarcinoma

Inclusion Criteria: 1. Patients older than the age of 18 years old at the time of study entry. 2. Patients with a body mass greater than 30 kg. 3. Patients with a pathological diagnosis of intrahepatic cholangiocarcinoma and at least one intrahepatic tumor measuring 3 cm in greatest dimension 4. Patients must have pathological or radiographic evidence of either: c. locally advanced unresectable iCCA - a multidisciplinary discussion should be documented for patients who have liver confined disease, confirming that the patient is not resectable. d. extrahepatic metastasis at the time of enrollment - allowable extrahepatic metastases may include disease in non-regional lymph nodes (note that metastatic involvement of regional lymph nodes in the hilum of the liver alone do not qualify as M1 disease), lung, and/or bone. 5. Patients should receive at least 4 cycles of systemic therapy with gemcitabine/cisplatin with durvalumab. If one of the drugs (gemcitabine/cisplatin/durvalumab) was held at any point for medical reasons during the initial 4 cycles, the patient is still eligible as long as the treating team agrees about the ability of the patient to continue systemic therapy. 6. Patients must be appropriate candidates for radiation therapy with adequate liver function, at the discretion of the treating physician. 7. A patient may pre-register at any time before cycle 4 of systemic therapy. To be eligible to pre-register for the trial, they must meet all other inclusion and exclusion criteria, except criteria number 5 regarding the number of cycles of systemic therapy.Pre-registration is not required to enroll. 8. Adequate normal organ and marrow function as defined below: Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 109 /L Platelet count ≥75 × 109/L Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 9. Must have a life expectancy of at least 12 weeks 10. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. Participation in another clinical study with an investigational product during the last 1 month. 2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 3. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than stated in the inclusion criteria. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 5. Major surgical procedure (as defined by the treating physician) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 6. History of allogenic organ transplantation. 7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3. Any chronic skin condition that does not require systemic therapy 4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician 5. Patients with celiac disease controlled by diet alone 8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart fa