This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.
Patients must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma (iCCA) that is resectable by imaging evaluation. Choice of staging modality is left up to the discretion of the treatment team; we favor high-quality CT scan of the chest/abdomen/pelvis with liver or biliary protocol. Eligibility will be confirmed through central imaging review.
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam.
Patients must be an acceptable risk surgical candidate at the time of enrollment, as determined by a board-certified surgeon with expertise in hepatobiliary surgery.
Tumor size > 5 cm.
Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent or biliary stents is acceptable.
Intranasal, inhaled, 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.
Single group
Biopsy Procedure
Procedure/SurgeryUndergo tissue biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cisplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT scan
Durvalumab
Biological/VaccineGiven IV
Gemcitabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI scan
Resection
Procedure/SurgeryUndergo surgical resection
Proportion of patients who complete 4 cycles of neoadjuvant therapy followed by surgical resection
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% confidence interval \[CI\]) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Major pathologic response (MPR) rate
MPR will be calculated based on the patients who can successfully undergo surgical resection. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Proportion of patients who attain an R0 margin status after surgical resection
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Radiological response rate
Defined as the percentage of patients with complete response, partial response, stable disease or progressive disease after neoadjuvant therapy by Response Evaluation Criteria in Solid Tumor (RECIST), modified RECIST and quantitative European Association for the Study of the Liver after completing 4 cycles of neoadjuvant therapy. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Overall survival (OS)
OS, including treatment-related, and disease-related death will be assessed using immune RECIST. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Kaplan-Meier method will be used to estimate the survival curves. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Tissue and blood based immune biomarkers
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Tumor genomics, transcriptional profile and multiplex immunohistochemistry and multiplex immunofluorescence
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Changes in circulating immune phenotypic profiles in the neoadjuvant phase
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Circulating tumor deoxyribonucleic acid-based minimal residual disease correlated with pathological response and RFS
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
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