Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorFrancesco De Cobelli

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 volunteers

Qualifiers

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

Design model

Single group

Treatments tested in this trial

  • radioembolization with Y-90

    Radiation

    Radioembolization with Y-90 will be performed in nominal day 0

  • Durvalumab

    Drug

    Following radioembolization, for 6 cycles -intravenous infusion on day 1 of each cycle

  • Cisplatin

    Drug

    Following radioembolization, for 6 cycles -intravenous infusion on day 1 and 8 of each cycle

  • Gemcitabine

    Drug

    Following radioembolization, for 6 cycles -intravenous infusion on day 1 and 8 of each cycle

Treatment groups

33 Participants
are divided into 1 treatment group
Group A: tretament armExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Overall response rate (ORR)

mRECIST criteria on imaging (modified Response Evaluation Criteria in Solid Tumors criteria)

Time frame
6 months post TARE
2

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Time frame
Through study completion, an average of 2 years

Secondary outcomes

1

Median progression free survival

mRECIST criteria

Time frame
Through study completion, an average of 12 months
2

Overall response rate

mRECIST criteria

Time frame
3 months post TARE
3

Overall response rate

RECIST 1.1 criteria

Time frame
3 months post TARE
4

Overall response rate

mRECIST

Time frame
Approximately 6 months post TARE

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

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