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

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative * 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 or extrahepatic cholangiocarcinoma or gallbladder cancer
• Documented metastatic disease on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
• Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
• Fully recovered from acute toxic effects (except alopecia, hearing loss, or non-clinically significant laboratory abnormalities) =< grade 1 of prior anti-cancer therapy
• Complete medical history and physical exam (performed within 28 days prior to day 1 of protocol therapy)
• Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 28 days prior to day 1 of protocol therapy)
• Platelets >= 100,000/mcL (performed within 28 days prior to day 1 of protocol therapy)
• Hemoglobin >= 8 g/dL (performed within 28 days prior to day 1 of protocol therapy)
• Serum albumin >= 2.8 g/dL (performed within 28 days prior to day 1 of protocol therapy)
• 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 of protocol therapy)
• Aspartate aminotransferase (AST) =< 5 x ULN (performed within 28 days prior to day 1 of protocol therapy)
• Alanine aminotransferase (ALT) =< 5 x ULN (performed within 28 days prior to day 1 of protocol therapy)
• Calculated creatinine clearance of >= 45 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy)
• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo (performed within 28 days prior to day 1 of protocol therapy) * If seropositive, patient may be eligible if they are stable on antiretroviral therapy, 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) and hepatitis C virus (HCV) tests (performed within 28 days prior to day 1 of protocol therapy) * For patients with active HBV, HBV deoxyribonucleic acid (DNA) < 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to day 1 of cycle 1, and willingness to continue anti-HBV treatment during the study (per standard of care) * If seropositive for HCV, nucleic acid quantification must be performed. Viral load 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) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential* to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy [or with a side effect of pregnancy prevention]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria

• Any prior systemic treatment for advanced cholangiocarcinoma or gallbladder cancer
• Any prior adjuvant therapy (chemotherapy, radiation therapy, biological therapy, immunotherapy) completed < 6 months prior to registration
• Prior exposure to immune-mediated therapy, including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Receipt of live attenuated vaccine within 30 days prior to the first dose of protocol therapy. Note that patients, if enrolled, should not receive live vaccine while receiving protocol therapy and up to 30 days after the last dose of protocol therapy
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: * Intranasal, inhaled, or topical steroids or local steroid injections (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Strong CYP3A4 inducers/inhibitors within 14 days prior to day 1 of protocol therapy
• Participation in another clinical study with an investigational product administered in the last 3 months
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Prior randomization or treatment in a previous durvalumab clinical study, regardless of treatment arm assignment
• 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 or spinal cord compression (including asymptomatic and adequately treated disease)
• 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 1 cycle 1 of treatment * Patients receiving prophylactic antibiotics are eligible, provided the signs of active 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 the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years
• History of allergic or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to study agents (platinum-based compounds, etc.)
• History of allogeneic organ transplantation
• History of active primary immunodeficiency
• Active and uncontrolled infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies)
• 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: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without an active disease in the last 5 years may be included but only after consultation with the study physician * Patients with celiac disease controlled by diet alone
• Clinically significant uncontrolled illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator’s judgment, contraindicate the patient’s participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)