About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Cancer classified as a combined or mixed type (HCC hepatocelular carcinoma and ICC) at screening -histopathological examination;
Child-Pugh class B or more or evidence of severe portal hypertension at screening or at any time up to and including baseline;
History of major gastrointestinal bleeding that required medical intervention within 30 days prior to screening or baseline;
Known hypersensitivity to tumor specific chemotherapy agents used during the study;
Trial design
Single group
Treatments tested in this trial
radioembolization with Y-90
RadiationRadioembolization with Y-90 will be performed in nominal day 0
Durvalumab
DrugFollowing radioembolization, for 6 cycles -intravenous infusion on day 1 of each cycle
Cisplatin
DrugFollowing radioembolization, for 6 cycles -intravenous infusion on day 1 and 8 of each cycle
Gemcitabine
DrugFollowing radioembolization, for 6 cycles -intravenous infusion on day 1 and 8 of each cycle
Treatment groups
Trial outcomes
Primary outcomes
Overall response rate (ORR)
mRECIST criteria on imaging (modified Response Evaluation Criteria in Solid Tumors criteria)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Secondary outcomes
Median progression free survival
mRECIST criteria
Overall response rate
mRECIST criteria
Overall response rate
RECIST 1.1 criteria
Overall response rate
mRECIST
Sponsors and contacts
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Francesco De Cobelli
Lead sponsor
IRCCS San Raffaele
Sponsor institution
Cardarelli Hospital
Collaborator
A.O. Ospedale Papa Giovanni XXIII
Collaborator
AOU Pisana, Pisa, Italy
Collaborator