Ignite Creation Date:
2025-12-25 @ 2:22 AM
Ignite Modification Date:
2025-12-27 @ 11:29 PM
Study NCT ID:
NCT06862934
Status:
RECRUITING
Last Update Posted:
2025-03-06
First Post:
2025-01-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018281', 'term': 'Cholangiocarcinoma'}, {'id': 'C562580', 'term': 'Cirrhosis, Familial, with Pulmonary Hypertension'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples and transplant specimens'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 14}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-03-20', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-03-03', 'studyFirstSubmitDate': '2025-01-27', 'studyFirstSubmitQcDate': '2025-03-03', 'lastUpdatePostDateStruct': {'date': '2025-03-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-03-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '3-year overall survival vs unresectable patients', 'timeFrame': '3 years', 'description': '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'}], 'secondaryOutcomes': [{'measure': '3-year recurrence-free survival vs unresectable patients', 'timeFrame': '3 years', 'description': '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'}, {'measure': '90-day morbidity', 'timeFrame': '90 days and long-term', 'description': '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'}, {'measure': 'Quality of life', 'timeFrame': '3 years', 'description': '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.'}, {'measure': '3-year OS vs resectable patients', 'timeFrame': '3 years', 'description': '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'}, {'measure': '3-year DFS vs resectable patients', 'timeFrame': '3 years', 'description': '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'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['liver transplantation', 'transarterial radioembolization', 'downstaging'], 'conditions': ['Intrahepatic Cholangiocarcinoma (Icc)']}, 'referencesModule': {'references': [{'pmid': '39544321', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nPatients 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).\n\nAfter 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.\n\nBoth 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.\n\nDuring 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.\n\nTumor response will be determined according to RECIST, mRECIST and Choi criteria.\n\nIn 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.\n\nAny 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)."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with unresectable liver-limited intrahepatic cholangiocarcinoma with no non-oncological contraindications to liver transplantation', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histological diagnosis of iCCA (biopsy-proven tumor)\n* Either first diagnosis or post-resection recurrence (occurring ≥ 6 months after resection)\n* 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).\n* Age between 18 and 70 years\n* 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)\n* No extrahepatic spread\n* Disease stability for at least 6 months\n* CA 19-9 \\< 200 u/ml at transplant listing in absence of jaundice\n* No medical and surgical contraindications to liver transplantation\n* Good performance status, Eastern Cooperative Oncology Group (ECOG) 0 or 1\n* No concomitant malignancies or history of other malignancies in the previous 5 years\n* Written informed consent\n\nExclusion Criteria:\n\n* Hilar and distal cholangiocarcinoma\n* Progression of disease under chemotherapy +/- radiation therapy, assessed with either RECIST, mRECIST or Choi criteria\n* Evidence of lymph-nodal metastases\n* Evidence of extrahepatic disease\n* Prior extrahepatic metastatic disease\n* Concomitant malignancies or history of other malignancies in the previous 5 years\n* Substance abuse, medical, psychological, or social conditions that may interfere with the patient\'s participation in the study or evaluation of the study results\n* Any reason why, in the opinion of the investigator, the patient should not participate to the study'}, 'identificationModule': {'nctId': 'NCT06862934', 'acronym': 'iCOLA', 'briefTitle': 'Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano'}, 'officialTitle': 'Liver Transplantation for Unresectable Intrahepatic Colangiocarcinoma After Sustained Response to Neoadjuvant Treatments (iCOLA)', 'orgStudyIdInfo': {'id': '253-24'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Transplant', 'description': 'Patients enrolled within the study who undergo downstaging and liver transplantation after with various combinations of chemotherapy +/- immunotherapy and TARE'}, {'label': 'Controls 1 (unresectable)', 'description': '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'}, {'label': 'Controls 2 (resectable)', 'description': 'Patients with resectable iCC who underwent curative-intent liver resection, matched to the transplanted patients using demographic characteristics, tumor burden and pre-surgical therapies'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20133', 'city': 'Milan', 'state': 'Milan', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Marianna Maspero, MD', 'role': 'CONTACT', 'email': 'marianna.maspero@istitutotumori.mi.it', 'phone': '0223904066', 'phoneExt': '+39'}, {'name': 'Vincenzo Mazzaferro, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Carlo Sposito, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marianna Maspero, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marco Bongini, MD, Ms', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Fondazione IRCCS Istituto Nazionale Tumori di Milano', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}], 'centralContacts': [{'name': 'Vincenzo Mazzaferro, MD, PhD', 'role': 'CONTACT', 'email': 'vincenzo.mazzaferro@istitutotumori.mi.it', 'phone': '0223902760', 'phoneExt': '+39'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione IRCCS Istituto Nazionale dei Tumori, Milano', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}