Cholangiocarcinoma, Liver Neoplasms
Conditions
Brief summary
This pilot clinical trial studies the safety and effectiveness of continuous hepatic arterial infusion (HAI) of floxuridine (FUDR) alone or in combination with other chemotherapeutic drugs in treating patients with locally advanced cholangiocarcinoma that cannot be removed by surgery. HAI is a method to deliver higher concentrations of FUDR more directly to liver tumors and reduces side effects. HAI alone or in combination with oxaliplatin and/or gemcitabine may significantly improve clinical outcomes of patients with locally advanced cholangiocarcinoma.
Interventions
DRUGFloxuridine
DRUGDexamethasone
DRUGGemcitabine
DRUGOxaliplatin
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have suspected intrahepatic or hilar cholangiocarcinoma with minimal extrahepatic disease. Diagnosis must be histologically or cytologically confirmed for continued treatment on study after pump placement. * Patient 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) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan/MRI * Patient must have disease that is unresectable or borderline resectable with \< 70% liver involvement by cancer * Patient must be \>= 18 years old. * Patient's Eastern Cooperative Oncology Group (ECOG) performance status must be =\< 2 (Karnofsky \>= 60%) * Patient must have normal organ and marrow function as defined below: * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 75,000/mcL * Total bilirubin =\< 2 mg/dL * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 5 X institutional upper limit of normal * Creatinine \<= institutional upper limit normal * Patient must be able to understand and willing to sign a written informed consent document
Exclusion criteria
* Patients must not have had prior treatment with FUDR * Patient must not be receiving any other investigational agents * Patient must not have a diagnosis of Gilbert's disease * Patient must not have a diagnosis of hepatic encephalopathy * Patient must not have had prior external beam radiation to the liver * Patient must not have a diagnosis of sclerosing cholangitis * Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patient must not be pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (DLTs) | Completion of 2 cycles of treatment by all patients (approximately 4 years) | Document the frequency of grades 3-5 non-hematologic toxicities (dose-limiting toxicities) associated with the treatment regimen by patient and by type of toxicity for each cohort during the first 2 cycles of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression (TTP) | 12 months | Describe median time to progression with a 95% confidence interval for each cohort. |
| Response rates | 8 weeks | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) Using RECIST 1.1 |
| Overall survival | 12 months | — |
| Number and grade of adverse events | Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months) | Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen. |
| Imaging biomarkers of tumor response | Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months) | Using magnetic resonance diffusion-weighted imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) before and during the course of treatment with HAI therapy, validate imaging biomarkers of tumor response |
Countries
United States
Outcome results
None listed