Single Arm, Multicenter Phase II Study Investigating the Efficacy and Safety of a Novel Therapeutic Scheme in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization in Combination With CisGem and Durvalumab (MEDI4736)
Underlying disease mechanisms are fundamental for correct treatment selection and patient management in highly invasive and debilitating non-transmissible diseases. Even though overall disease burden of cancer may have decreased due to a higher degree of awareness, the availability of high-quality healthcare and early diagnosis may become challenging in certain neoplasms. Cholangiocarcinoma is usually diagnosed at advanced stages due to non-specific presentation and is frequently refractory to chemotherapy, causing a massive impact on patients and their families. Surgery is currently the only curative treatment but is available to only approximately 30% of patients. The combination of interventional- and immune-oncology to standard of care creates the perfect substrate for synergistic mechanisms to fight tumor growth; in situ cell death following transarterial embolization(TARE) elicits immune mediated response, inflammatory response and biomarkers of oxidative stress and increases antigen presenting T-cells which an anti-anti progam death ligand (PD-L)1 can bind to; standard of care can then add on with its known effects.The rationale of a combined- locoregional and systemic - treatment lies in the synergistic effects of each of the treatments.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (European Union \[EU\] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol related procedures, including screening evaluations.
• Patients with liver predominant intrahepatic cholangiocarcinoma with intermediate/high rate of early recurrence calculated according to https://k-sahara.shinyapps.io/Veryearlyrecurrence/.
• Patients aged \> 18 to ≤ 80 at time of study entry;
• Body weight \>30kg
• Suspicion or biopsy confirmed diagnosis of iCC, not previously treated with systemic or surgical therapies, including not previously enrolled in another clinical study with an investigational product;
• Preserved liver function as defined as: Child Pugh Class A; Model for End Stage Liver Disease Score (MELD) \<10; Future Liver Remnant (FLR) uptake function ≥2.7%/min/m2 on technetium- 99m mebrofenin hepatobiliary scintigraphy and FLR volume\> 30% of total functional liver volume for a normal liver, or \> 40% of total functional liver volume if the liver has been damaged by chronic liver disease, cholestasis, steatohepatitis or diabetes;
• No technical contraindications to TARE as confirmed by pre-procedural angiographic and scintigraphy;
• DNA tests for hepatitis B virus (HBV) and RNA tests for hepatitis C virus (HCV) negative at Screening;
• Adequate heart and lung function;
• Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1;
• Adequate renal and hepatic function as indicated by: serum creatinine \<2x upper limit of normal and estimated glomerular filtration rate (eGFR) ≥30ml/min or 1.73m2; measured creatinine clearance (CL) \>40 mL/min or calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976\*) or by 24-hour urine collection for determination of creatinine clearance; Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal (ULN) and total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician);
• Hemoglobin ≥9 g/dL, platelet count ≥75,000/mm3, absolute neutrophil count (ANC) ≥ 1.0 x 109 /L
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks