Unresectable intrahepatic cholangiocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10073077 Term: Intrahepatic cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Gemcitabina
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: GEMCITABINA
Current Sponsor code: NA
Concentration unit: mg/ml milligram(s)
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Suspected or biopsy-confirmed diagnosis of intrahepatic cholangiocarcinoma (ICC), not previously treated with systemic or surgical therapies; - Preserved liver function, defined as: Child Pugh Class A; MELD score (Model forEnd Stage Liver Disease Score} 30ml/min or 1.73m/2; alkaline phosphatase (ALP}, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST} s 5 times the upper limit of normal (ULN) and total bilirubin s 2.0 mg/dl; - Hemoglobin greater than or equal to10 g/dL, platelet count greater than or equal to 70,000/mm3, absolute neutrophil count >1500/mm3. - Ability and willingness to provide written informed consent and to comply with study protocol and procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: • Pregnant or breastfeeding women; - Uncorrectable coagulopathies - Extensive disease extrahepatic or extrarenal - Tumor classified as combined or mixed type (HCC and ICC} at screening - Child-Pugh Class B or higher or evidence of severe portal hypertension at screening or at any time up to and including baseline; - History of major gastrointestinal bleeding requiring medical attention within 30 days prior to screening or at baseline; - Known hypersensitivity to the specific chemotherapy agents used during the study; - Any oral or parenteral chemotherapy or immunotherapy treatment within 2 years prior to screening; - Previous allogeneic bone marrow transplant, kidney or legacy transplant; - Active viral, bacterial or fungal infections, clinically relevant to the assessment of fitness; - Current history or evidence of neuropsychiatric illness, including depression, schizophrenia, bipolar disorder, impaired cognition, dementia, or suicidal tendencies; - History of serious cardiovascular disease, such as a previous stroke, coronary artery disease requiring surgery, or unresolved arrhythmias within the last 6 months. - Evidence of any hematologic malignancy; - Positive to human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2) (serum or RNA} and/or hepatitis B virus surface antigen (HBsAg} and/or active infection with Treponema Pallidum or Mycoplasma; - Abuse of alcohol in the 2 months prior to the study or abuse of any substance in the 6 months prior to the study; - Known bleeding diathesis or history of abnormal bleeding or any other known coagulation abnormality that may contraindicate future surgery or biopsies; - Use of immunosuppressant steroids (prednisone equivalent > 10 mg/day}; - Presence of hepatopulmonary shunt >20% or other contraindications to arterial radioembolization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess efficacy-defined as overall response rate - of radioembolization (TARE) followed by a combination of standard of care chemotherapy with cisplatin and gemcitabine plus durvalumab in patients with liver predominant unresectable intrahepatic cholangiocarcinoma and assess the safety of the therapeutic scheme. This study will administer durvalumab out of its current indication (indication for first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC) approved by the FDA on September 2, 202; positive opinion given by EMA's Committee for Medicinal Products for Human Use (CHMP) for the same indication awaiting European Commission Approval). Radioembolization will be performed using SIR-Spheres® resin Microspheres (loaded with yttrium-90 ) code SIR-Y001; an approved class II medical device device (145685IR) outside its indication for use for which a request to initiate an investigation will be sent to the Ministry of Health.;Secondary Objective: Describe tumor biological aspects; Investigate the relationship between tumor circulating markers, tumor tissue based markers,quantitative non-invasive imaging and radiomics-based parameters, genetic markers in tissue and biological substrates; Evaluate tumor mutational burden, immunological landscape in responders and non-responders to treatment at given time points and among time points; Quantitative imaging based parameters in responders and non-responders at given time points and among time points; Interim assessment of efficacy of treatment regimen.;Primary end point(s): Efficacy: Overall response rate (ORR) according to mRECIST 1.1 criteria on imaging Safety: Evaluate adverse events, laboratory findings, vital signs and other diagnostic evaluation alterations;Timepoint(s) of evaluation of this end point: Efficacy: at six (6) months after radioembolization (TARE). Safety: throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Describe tumor biological aspects: Investigate the relationship between tumor circulating markers, tumor tissue based markers; quantitative non-invasive imaging and radiomics-based parameters; genetic markers in tissue and biological substrates; Describe the tumor microenvironment (tissue and circulating biomarkers, quantitative imaging, immune response) correlate these with response to treatment; distinguish characteristics of responders vs non-responders;; Efficacy: interim evaluation of treatment response defined as overall response rate according to mRECIST 1.1 e RECIST;Timepoint(s) of evaluation of this end point: Serial blood sampling; cytokine profiling - baseline, at approximately one month ( pre-systemic treatment), at three months post TARE Biopsy prior to and following treatment - baseline and at three months post TARE Imaging: protocol defined imaging time points basal, at one month, three months, six months post TARE and at imaging time points during follow up; Data collected during the study; evaluation against imaging at 3 and 6 months - overall evaluation at the end of the treatment period; Imaging at three months after radioembolizzation (TARE) | — |
Countries
Italy
Contacts
Public ContactCRO
Aleph
Outcome results
None listed