Intrahepatic Cholangiocarcinoma (Icc)iCOLANCT06862934
Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments
An observational study of Intrahepatic Cholangiocarcinoma (Icc), run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
This is single-arm, observational, academic, investigator-driven study investigating the efficacy of liver transplantation after successful and sustained downstaging/tumor control of liver-limited unresectable intrahepatic cholangiocarcinoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma (Icc)
- How many people
- 14 participants
- Where
- 1 siteItaly
- Study dates
- 20 Mar 2025to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with unresectable liver-limited intrahepatic cholangiocarcinoma with no non-oncological contraindications to liver transplantation
Who may be able to join
- Histological diagnosis of iCCA (biopsy-proven tumor)
- Either first diagnosis or post-resection recurrence (occurring ≥ 6 months after resection)
- Unresectability assessment due to tumor location (leading to insufficient live remnant with/out implementation of hypertrophic parenchymal techniques) or underlying liver disease. Non-resectability assessed by an expert surgical team with experience on both resection and transplantation (centralized at INT Milan).
- Age between 18 and 70 years
- No macrovascular tumor invasion (NB: portal vein and/or hepatic vein occlusion from the external tumor compression and classified as "encasement" could be considered after expert radiology review)
- No extrahepatic spread
Show all 12Show fewer
- Disease stability for at least 6 months
- CA 19-9 < 200 u/ml at transplant listing in absence of jaundice
- No medical and surgical contraindications to liver transplantation
- Good performance status, Eastern Cooperative Oncology Group (ECOG) 0 or 1
- No concomitant malignancies or history of other malignancies in the previous 5 years
- Written informed consent
Who cannot join
- Hilar and distal cholangiocarcinoma
- Progression of disease under chemotherapy +/- radiation therapy, assessed with either RECIST, mRECIST or Choi criteria
- Evidence of lymph-nodal metastases
- Evidence of extrahepatic disease
- Prior extrahepatic metastatic disease
- Concomitant malignancies or history of other malignancies in the previous 5 years
- Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any reason why, in the opinion of the investigator, the patient should not participate to the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Nazionale Tumori di Milano
Milan, Milan, 20133
Marianna Maspero, MD, 0223904066 ext. +39, marianna.maspero@istitutotumori.mi.it
Vincenzo Mazzaferro, MD, PhD
About this study
Official title: Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments (iCOLA)
This is single-arm, observational, academic, investigator-driven study investigating the efficacy of liver transplantation after successful and sustained downstaging/tumor control of liver-limited unresectable intrahepatic cholangiocarcinoma. The downstaging protocol includes chemotherapy +/- immunotherapy and transarterial radioembolization (TARE) with Yttrium-90 in various combinations.
Read the detailed description
This is a single-arm, observational, academic, investigator-driven study investigating the efficacy of liver transplantation after successful and sustained downstaging/tumor control of liver-limited unresectable intrahepatic cholangiocarcinoma.
Patients with biopsy-proven unresectable ICC who fit within inclusion criteria will be enrolled in the study. Patients with unresectable ICC who enter the protocol with an intention-to-treat strategy will first undergo CT scan +/- MRI, FDG-PET and staging laparoscopy with nodal sampling at the hepatic hilum (at least stations 8 and 12). In case of negative staging (no peritoneal carcinomatosis, no tumor spread in lymph nodes, negative tumor citology in the peritoneal washing), they will receive downstaging with state-of-the-art chemotherapy +/- immune checkpoint inhibitors (ICIs) (at the time of writing: gemcitabine-cisplatin +/- durvalumab) for 2 cycles, followed by transarterial radioembolization with Y90 (Y90-TARE), followed by at least 4 other cycles of gemcitabine-cisplatin +/- durvalumab. If actionable mutations are present at gene sequencing of tumoral tissue are present, molecular-targeted treatments with FGFR-inhibitors, IDH-1 inhibitors and PARP-inhibitors are allowed after multidisciplinary evaluations. Patients who cannot undergo Y90-TARE due to absolute contraindications (e.g., evidence of pulmonary shunts at angioscintigraphy) may be considered for stereotactic body radiation therapy (SBRT).
After downstaging, patients will undergo disease restaging with CT scan +/- MRI, FDG-PET and CA19-9 and, if at least tumor stability is confirmed with CA19-9 < 200 u/ml, they will undergo transplant screening and listing.
Both naive patients and patients already receiving systemic and/or locoregional therapies for their unresectable ICC are eligible as long as sustained response is demonstrated. In all instances, they will undergo staging laparoscopy and, if negative (see above) with at least 6 months of tumor stability from diagnosis, they will go directly to transplant screening and listing.
During listing, restaging will be performed every two months with CT scan and/or MRI, molecular markers and FDG-PET. Maintenance therapy is allowed at the discretion of the patient's oncology team. The target interval between listing and transplant should be less than 90 days.
Tumor response will be determined according to RECIST, mRECIST and Choi criteria.
In case of disease progression during listing, the patient will be suspended from the transplant waiting list. Re-listing is allowed after second-line therapy if disease stability for at least four months if achieved, at the discretion of the multidisciplinary tumor and transplant board of INT Milan.
Any kind of donor will be considered as suitable for the recruited patients, including marginal marginal organ donation (DCD, split-liver, age >75, severe steatosis, etcetera).
- Conditions
- Intrahepatic Cholangiocarcinoma (Icc)
- Keywords
- liver transplantation, transarterial radioembolization, downstaging
- Medical subject headings
- Cholangiocarcinoma, Cirrhosis, Familial, with Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Transplant | Patients enrolled within the study who undergo downstaging and liver transplantation after with various combinations of chemotherapy +/- immunotherapy and TARE | |
| Controls 1 (unresectable) | Historical controls with the same inclusion criteria as the iCOLA protocol, treated with systemic and locoregional therapies and prospectively recruited patients with tumor response who refused transplantation or were not found eligible to LT for medical/non-oncological conditions | |
| Controls 2 (resectable) | Patients with resectable iCC who underwent curative-intent liver resection, matched to the transplanted patients using demographic characteristics, tumor burden and pre-surgical therapies |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year overall survival vs unresectable patients
OS at 3 years after liver transplant will be matched and compared with OS of patients with similar characteristics that were not offered LT, taken from an institutional historical series and from patients found not eligible to LT due to medical/non-oncological conditions
Measured: 3 years
Secondary outcomes (5)
3-year recurrence-free survival vs unresectable patients
To evaluate the time to recurrence after LT in patients with unresectable iCCA, RFS at 3 years after LT will be matched and compared with time to progression of patients with similar characteristics that were not offered LT, taken from an institutional historical series and from patients found non-eligible to LT due to medical/non-oncological conditions
Measured: 3 years
90-day morbidity
The safety of chemotherapy +/- immunotherapy, locoregional treatments and liver transplatation in patients with unresectable iCCA will be assessed with the Clavien-Dindo classification and the Comprehensive Complication Index
Measured: 90 days and long-term
Quality of life
The impact of this treatment strategy and of LT on quality of life in patients with unresectable iCCA 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.
Measured: 3 years
3-year OS vs resectable patients
OS after LT in patients with unresectable iCCA will be compared with OS of patients with similar characteristics, but with resectable tumors, who underwent surgical resection during the same time period
Measured: 3 years
3-year DFS vs resectable patients
DFS after LT in patients with unresectable iCCA will be compared with DFS of patients with similar characteristics, but with resectable tumors, who underwent surgical resection during the same time period
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start20 Mar 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intrahepatic Cholangiocarcinoma (Icc)Studies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06862934
- Sponsor's protocol ID
- 253-24
- Acronym
- iCOLA
- Status last verified
- Jan 2025
- First submitted
- 27 Jan 2025
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Maspero M, Sposito C, Bongini MA, Cascella T, Flores M, Maccauro M, Chiesa C, Niger M, Pietrantonio F, Leoncini G, Bellia V, Bhoori S, Mazzaferro V. Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study. Transpl Int. 2024 Oct 31;37:13641. doi: 10.3389/ti.2024.13641. eCollection 2024.
PubMed 39544321Blair AB, Alobuia WM, Palta M, Raman SS, Levine MH, Benson AB 3rd, D'Angelica MI, Cloyd JM. Locoregional Treatment Options for Locally Advanced Intrahepatic Cholangiocarcinoma. J Natl Compr Canc Netw. 2025 Aug 14;23(9):e257085. doi: 10.6004/jnccn.2025.7085.
PubMed 40812353
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments (iCOLA)
- ClinicalTrials.gov ID
- NCT06862934
- Acronym / sponsor ID
- iCOLA / 253-24
- Conditions
- Intrahepatic Cholangiocarcinoma (Icc)
- Keywords
- liver transplantation, transarterial radioembolization, downstaging
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 20 Mar 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 6 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is single-arm, observational, academic, investigator-driven study investigating the efficacy of liver transplantation after successful and sustained downstaging/tumor control of liver-limited unresectable intrahepatic cholangiocarcinoma. The downstaging protocol includes chemotherapy +/- immunotherapy and transarterial radioembolization (TARE) with Yttrium-90 in various combinations.
Detailed description
This is a single-arm, observational, academic, investigator-driven study investigating the efficacy of liver transplantation after successful and sustained downstaging/tumor control of liver-limited unresectable intrahepatic cholangiocarcinoma.
Patients with biopsy-proven unresectable ICC who fit within inclusion criteria will be enrolled in the study. Patients with unresectable ICC who enter the protocol with an intention-to-treat strategy will first undergo CT scan +/- MRI, FDG-PET and staging laparoscopy with nodal sampling at the hepatic hilum (at least stations 8 and 12). In case of negative staging (no peritoneal carcinomatosis, no tumor spread in lymph nodes, negative tumor citology in the peritoneal washing), they will receive downstaging with state-of-the-art chemotherapy +/- immune checkpoint inhibitors (ICIs) (at the time of writing: gemcitabine-cisplatin +/- durvalumab) for 2 cycles, followed by transarterial radioembolization with Y90 (Y90-TARE), followed by at least 4 other cycles of gemcitabine-cisplatin +/- durvalumab. If actionable mutations are present at gene sequencing of tumoral tissue are present, molecular-targeted treatments with FGFR-inhibitors, IDH-1 inhibitors and PARP-inhibitors are allowed after multidisciplinary evaluations. Patients who cannot undergo Y90-TARE due to absolute contraindications (e.g., evidence of pulmonary shunts at angioscintigraphy) may be considered for stereotactic body radiation therapy (SBRT).
After downstaging, patients will undergo disease restaging with CT scan +/- MRI, FDG-PET and CA19-9 and, if at least tumor stability is confirmed with CA19-9 < 200 u/ml, they will undergo transplant screening and listing.
Both naive patients and patients already receiving systemic and/or locoregional therapies for their unresectable ICC are eligible as long as sustained response is demonstrated. In all instances, they will undergo staging laparoscopy and, if negative (see above) with at least 6 months of tumor stability from diagnosis, they will go directly to transplant screening and listing.
During listing, restaging will be performed every two months with CT scan and/or MRI, molecular markers and FDG-PET. Maintenance therapy is allowed at the discretion of the patient's oncology team. The target interval between listing and transplant should be less than 90 days.
Tumor response will be determined according to RECIST, mRECIST and Choi criteria.
In case of disease progression during listing, the patient will be suspended from the transplant waiting list. Re-listing is allowed after second-line therapy if disease stability for at least four months if achieved, at the discretion of the multidisciplinary tumor and transplant board of INT Milan.
Any kind of donor will be considered as suitable for the recruited patients, including marginal marginal organ donation (DCD, split-liver, age >75, severe steatosis, etcetera).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Transplant | – | –Patients enrolled within the study who undergo downstaging and liver transplantation after with various combinations of chemotherapy +/- immunotherapy and TARE |
| Controls 1 (unresectable) | – | –Historical controls with the same inclusion criteria as the iCOLA protocol, treated with systemic and locoregional therapies and prospectively recruited patients with tumor response who refused transplantation or were not found eligible to LT for medical/non-oncological conditions |
| Controls 2 (resectable) | – | –Patients with resectable iCC who underwent curative-intent liver resection, matched to the transplanted patients using demographic characteristics, tumor burden and pre-surgical therapies |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with unresectable liver-limited intrahepatic cholangiocarcinoma with no non-oncological contraindications to liver transplantation
Key inclusion criteria (12 listed)
- Histological diagnosis of iCCA (biopsy-proven tumor)
- Either first diagnosis or post-resection recurrence (occurring ≥ 6 months after resection)
- Unresectability assessment due to tumor location (leading to insufficient live remnant with/out implementation of hypertrophic parenchymal techniques) or underlying liver disease. Non-resectability assessed by an expert surgical team with experience on both resection and transplantation (centralized at INT Milan).
- Age between 18 and 70 years
- No macrovascular tumor invasion (NB: portal vein and/or hepatic vein occlusion from the external tumor compression and classified as "encasement" could be considered after expert radiology review)
Key exclusion criteria (8 listed)
- Hilar and distal cholangiocarcinoma
- Progression of disease under chemotherapy +/- radiation therapy, assessed with either RECIST, mRECIST or Choi criteria
- Evidence of lymph-nodal metastases
- Evidence of extrahepatic disease
- Prior extrahepatic metastatic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
3-year overall survival vs unresectable patients
Time frame: 3 years
OS at 3 years after liver transplant will be matched and compared with OS of patients with similar characteristics that were not offered LT, taken from an institutional historical series and from patients found not eligible to LT due to medical/non-oncological conditions
5 secondary outcomes
3-year recurrence-free survival vs unresectable patients
Time frame: 3 years
90-day morbidity
Time frame: 90 days and long-term
Quality of life
Time frame: 3 years
3-year OS vs resectable patients
Time frame: 3 years
3-year DFS vs resectable patients
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Background: PubMed 39544321Maspero M, Sposito C, Bongini MA, Cascella T, Flores M, Maccauro M, Chiesa C, Niger M, Pietrantonio F, Leoncini G, Bellia V, Bhoori S, Mazzaferro V. Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study. Transpl Int. 2024 Oct 31;37:13641. doi: 10.3389/ti.2024.13641. eCollection 2024.
- Derived from this study: PubMed 40812353Blair AB, Alobuia WM, Palta M, Raman SS, Levine MH, Benson AB 3rd, D'Angelica MI, Cloyd JM. Locoregional Treatment Options for Locally Advanced Intrahepatic Cholangiocarcinoma. J Natl Compr Canc Netw. 2025 Aug 14;23(9):e257085. doi: 10.6004/jnccn.2025.7085.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intrahepatic Cholangiocarcinoma (Icc), run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincenzo Mazzaferro, MD, PhD (0223902760 ext. +39, vincenzo.mazzaferro@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year overall survival vs unresectable patients (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06862934, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.