Preoperative Nab-paclitaxel, Cisplatin, and Gemcitabine Chemotherapy With or Without Infigratinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, The OPTIC Trial

Inclusion Criteria:

* Diagnosis of intrahepatic cholangiocarcinoma
* High-quality cross-sectional imaging by computerized tomography (CT) or magnetic resonant imaging (MRI) performed within 6 weeks prior to enrollment and showed a resectable IHCCA confined to the liver, bile duct, and /or regional lymph nodes. No distant extrahepatic disease is allowed.
* Adults \> 18 years of age
* Able to give informed consent
* Able to adhere to study visit schedule and other protocol requirements
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Adequate bone marrow reserves as evidenced by:
* Absolute neutrophil count (ANC) ≥1,500 cells/ul
* Platelet count ≥100,000 cells/μl
* Hemoglobin ≥9 g/dL
* Adequate hepatic function as evidenced by:
* Serum total bilirubin ≤1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN
* Albumin ≥3 g/dl
* Adequate renal function as evidenced by creatinine ≤1.5 x ULN
* Creatinine =\< 1.5 x ULN
* Have amylase or lipase \< 2.0 x ULN
* Male, or a non-pregnant and non-lactating female
* Women of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]) must commit to true abstinence from heterosexual contact, or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/cisplatin/nab- paclitaxel (including dose interruptions) until treatment with gemcitabine/cisplatin/nab-paclitaxel is complete.
* Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/cisplatin/nab-paclitaxel and for 6 months following gemcitabine/cisplatin/nab- paclitaxel is continuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

* Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)".
* Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
* Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.
* Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
* Have current evidence of concerning endocrine alterations of calcium/phosphate homeostasis, eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc, in the opinion of the investigator.
* Have abnormal calcium or phosphorus, or calcium-phosphorus product ≥55 mg\^2 /dL2:

  * Inorganic phosphorus above local normal limits
  * Total corrected serum calcium above local normal limits
* Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
* Have clinically significant cardiac disease including any of the following: a. Congestive heart failure requiring treatment (New York Heart Association Grade ≥2), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines (Williams et al 2018)
* Fridericia's correction formula QTcF \>470 msec (males and females). Note: If the QTcF is \>470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard
* Known history of congenital long QT syndrome
* Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations.
* Pregnancy (positive pregnancy test) or lactation.
* Known CNS disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
* Previous (within the past 3 years) or concurrent presence of other cancer, except non-melanoma skin cancer, renal cell carcinoma \< 3cm, neuroendocrine tumors \< 2cm, and in situ carcinomas including bronchoalveolar carcinoma (BAC).
* History of allergy or hypersensitivity to any of the study drugs.
* Current abuse of alcohol or illicit drugs.
* Inability or unwillingness to sign the informed consent form.