Klatskin Tumor, Perihilar Cholangiocarcinoma
Conditions
Keywords
liver transplantation, stereotactic body radiation therapy, downstaging
Brief summary
This is multicentric, single-arm, observational, investigator-drive study investigating the efficacy of liver transplantation after successful downstaging/disease control of unresectable perihilar cholangiocarcinoma using chemotherapy +/- immunotherapy and stereotactic body radiation therapy (SBRT).
Detailed description
Patients with unresectable pCCA who fit within inclusion criteria will be enrolled in the study. They will undergo staging laparoscopy with nodal sampling at the hepatic hilum. In case of negative staging (no peritoneal carcinomatosis, no positive hilar lymph nodes, negative peritoneal washing), they will receive downstaging with gemcitabine-cisplatin +/- durvalumab for 2 cycles, followed by SBRT, followed by at least 4 other cycles of gemcitabine-cisplatin +/- durvalumab. After downstaging, they will undergo disease restaging and, if at least disease stability is confirmed, they will undergo transplant screening and listing. Treatment with gemcitabine-cisplatin + durvalumab will continue until liver transplant, progression or unacceptable toxicity. During listing, restaging will be performed every two months with CT scan and/or MRI, molecular markers and FDG-PET. The target interval between listing and transplant should be less than 90 days.
Interventions
None listed
Sponsors
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of unresectable peripheral cholangiocarcinoma arising one centimeter or more above the superior pancreatic margin, with tumor diameter ≤ 3 cm, diagnosed by: * Transcatheter biopsy or brush cytology * CA-19.9 \> 100 mg/ml and/or a mass on cross-sectional imaging with a malignant appearing stricture on cholangiography * Biliary ploidy by FISH with a malignant appearing stricture on cholangiography * Age between 18 years and 70 years * Absence of intra- and extrahepatic metastases * Absence of lymph-nodal metastases at any site * Biliary stenting of all liver districts * No contraindications to liver transplantation * No concomitant malignancies or history of other malignancies in the previous 5 years * Written informed consent
Exclusion criteria
* Intrahepatic cholangiocarcinoma * Uncontrolled infection * Concomitant malignancies or history of other malignancies in the previous 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year overall survival | 3 years | To evaluate overall survival at 36 months in patients with unresectable hilar cholangiocarcinoma treated with neoadjuvant chemotherapy and SBRT followed by liver transplantation according to the modified Mayo Clinic protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-year recurrence-free survival | 3 years | To evaluate recurrence-free survival at 36 months in patients with unresectable hilar cholangiocarcinoma treated with neoadjuvant chemotherapy and SBRT followed by liver transplantation according to the modified Mayo Clinic protocol |
| Safety and feasibility | 3 years | To evaluate the safety and feasibility of neoadjuvant SBRT and chemotherapy in patients with unresectable hilar cholangiocarcinoma candidate to liver transplantation, in particular we will describe in detail the therapeutic path of all patients with unresectable pCCA that enter within the downstaging pathway and are evaluated for LT, how many are able to be transplanted within this protocol, and what are the reasons for dropout from the protocol |
| Quality of life | 3 years | To evaluate the impact of this treatment strategy and of LT on quality of life in patients with unresectable pCCA. Quality of life will be assessed with validated questionnaires. Questionnaires will be performed at baseline and at 6 months intervals; they will be matched and compared with that of eligible patients recruited within the same study period and receiving non-transplant treatments |
Countries
Italy
Contacts
Primary ContactVincenzo Mazzaferro, MD, PhD
Outcome results
None listed