Pressurized Intraperitoneal Aerosolized Nab-Paclitaxel in Combination With Gemcitabine and Cisplatin for the Treatment of Biliary Tract Cancer Patients With Peritoneal Metastases

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

• If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Histologically or cytologically confirmed intrahepatic cholangiocarcinoma orextrahepatic cholangiocarcinoma or gallbladder cancer

• Documented metastatic disease on computed tomography (CT) imaging or magneticresonance imaging (MRI). CT scan or MRI to assess measurable disease must have beencompleted within 28 days prior to registration

• Visible peritoneal metastatic disease on cross-sectional imaging or diagnosticlaparoscopy (does not have to be measurable by Response Evaluation Criteria in SolidTumors [RECIST] 1.1)

• Fully recovered from acute toxic effects (except alopecia, hearing loss, ornon-clinically significant laboratory abnormalities) =< grade 1 of prior anti-cancertherapy

• Complete medical history and physical exam (performed within 28 days prior to day 1of protocol therapy unless otherwise stated)

• Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Platelets >= 100,000/mcL (performed within 28 days prior to day 1 of protocoltherapy unless otherwise stated)

• Hemoglobin >= 8 g/dL (performed within 28 days prior to day 1 of protocol therapyunless otherwise stated)

• Serum albumin >= 2.8 g/dL (performed within 28 days prior to day 1 of protocoltherapy unless otherwise stated)

• Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease,then direct bilirubin < 1.5 mg/dL) (performed within 28 days prior to day 1 ofprotocol therapy unless otherwise stated)

• Aspartate aminotransferase (AST) =< 5 x ULN (performed within 28 days prior to day 1of protocol therapy unless otherwise stated)

• Alanine aminotransferase (ALT) =< 5 x ULN (performed within 28 days prior to day 1of protocol therapy unless otherwise stated)

• Calculated creatinine clearance of >= 45 mL/min per 24 hour urine test or theCockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapyunless otherwise stated)

• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo (performed within 28 days prior to day 1 of protocol therapy unless otherwisestated)

• If seropositive, patient may be eligible if they are stable on antiretroviraltherapy, have a CD4 T cell count >= 200/µL, and have an undetectable viral load

• Documented virology status of hepatitis, confirmed by hepatitis B virus (HBV) andhepatitis C virus (HCV) tests (performed within 28 days prior to day 1 of protocoltherapy unless otherwise stated)

• For patients with active HBV, HBV deoxyribonucleic acid (DNA) < 500 IU/mLduring screening, initiation of anti-HBV treatment at least 14 days prior today 1 of cycle 1, and willingness to continue anti-HBV treatment during thestudy (per standard of care)

• If seropositive for HCV, nucleic acid quantification must be performed. Viralload must be undetectable

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 28 days prior to day 1 of protocol therapy unless otherwisestated)

• If the urine test is positive or cannot be confirmed as negative, a serumpregnancy test will be required

• Agreement by females and males of childbearing potential* to use an effective methodof birth control (e.g. licensed hormonal/barrier methods or surgery intended toprevent pregnancy [or with a side effect of pregnancy prevention]) or abstain fromheterosexual activity for the course of the study through at least 14 months afterthe last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Any prior systemic therapy treatment for advanced cholangiocarcinoma or gallbladdercancer

• Any prior adjuvant therapy (chemotherapy, radiation therapy, biological therapy,immunotherapy) completed < 6 months prior to registration

• Strong CYP3A4 inducers/inhibitors within 14 days prior to day 1 of protocol therapy

• Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy,or exclusive total parenteral nutrition

• Evidence of liver metastases with >= 50% liver occupation

• Any history of, or current, brain or subdural metastases

• Life expectancy < 3 months

• History of peripheral neuropathy >= grade 2 measured by NCI CTCAE version 5.0 ("moderate symptoms, limiting instrumental activities of daily living")

• Treatment with therapeutic oral or IV antibiotics within 14 days prior to day 1cycle 1 of treatment

• Patients receiving prophylactic antibiotics are eligible, provided the signs ofactive infection have resolved

• Any prior malignancy except adequately treated basal or squamous cell skin cancer,in situ cervical cancer, adequately treated stage I or II cancer from which thepatient is currently in complete remission, or any other cancer from which thepatient has been disease-free for two years

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study agents (platinum-based compounds, etc.)

• Clinically significant uncontrolled illness

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)