TREMELIMUMAB for Locally advanced cholangiocarcinoma | Cholangiocarcinoma

Inclusion criteria

• {"criterion_text":"- 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 (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.\n- Histologically or pathologically confirmed CCA.\n- Age >18 years at time of study entry.\n- Eastern Cooperative Oncology Group (ECOG) 0 or 1.\n- Initially unresectable CCA (as assessed in multidisciplinary sessions). Patients, in the absence of extrahepatic disease or hilar cholangiocarcinoma, are defined as \"initially unresectable\" for one or more of the following conditions at CT-based radiologic staging: - Tumor adjacent to the remaining liver; - Tumor adjacent or infiltrating the portal vein; - Tumor with up to three contralateral metastases in the remaining liver; - Loco-regional lymphnodes involvement.\n- Life expectancy of at least 16 weeks.\n- Body weight >30 kg\n- Adequate normal organ and marrow function as defined below: - Haemoglobin ≥9.0 g/dL; - Absolute neutrophil count (ANC ≥1.5 × 109 /L); - Platelet count ≥100 × 109/L; - Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician; - AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN; - Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance; - At least 1 lesion that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization; - No previous systemic or local treatments including radiation therapy, radiofrequency ablations, electro-chemotherapy."}

Exclusion criteria

• {"criterion_text":"- Any previous participation in another clinical interventional study.\n- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); - Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent; - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication); - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP; - Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab and tremelimumab combination therapy; - Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients; - Known allergy or hypersensitivity to IP or any excipient.\n- Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.\n- History of allogenic organ transplantation.\n- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Local surgery of isolated lesions for palliative intent is acceptable.\n- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, interstitial lung disease, etc.]). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia; b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; c. Any chronic skin condition that does not require systemic therapy; d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician; e. Patients with celiac disease controlled by diet alone\n- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction within 12 months, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.\n- History of bowel obstruction, refractory ascites, or bowel perforation due to advanced disease within the past 3 months from start of study treatment.\n- Significant bleeding diathesis or coagulopathy. Serious, nonhealing wound, ulcer, or current healing fracture.\n- History of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence; b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c. Adequately treated carcinoma in situ without evidence of disease"}

Primary endpoints

• {"endpoint_text":"- For the primary endpoint the proportion of CCA at 12 months after surgery will be computed along with an exact 90% confidence interval (CI). A one-sided exact test with a significance level of 0.05 will be performed assuming a H0 of the proportion of CCA at 12 months equal to 0.512. The safety analyses will be carried out on the SP. All the information necessary to identify the appearance of adverse events will be used in the analysis and summarized through descriptive statistics.","definition_or_measurement_approach":"Proportion of cholangiocarcinoma (CCA) at 12 months after surgery; compute proportion with exact 90% CI; perform one-sided exact test (alpha=0.05) against H0 = 0.512. Safety summarised using descriptive statistics; adverse events identified and summarised."}

Secondary endpoints

• {"endpoint_text":"- For secondary endpoints summary statistics will be calculated and reported along with 95% CI. Time-to event variables (PFS and OS) will be analyzed using the Kaplan-Meier product limit method (KM) and survival curves will be reported along with 95% CI.","definition_or_measurement_approach":"Secondary endpoints summarised with summary statistics and 95% CI. Time-to-event endpoints (Progression Free Survival and Overall Survival) analysed by Kaplan-Meier method; survival curves reported with 95% CI."}

Italy

Earliest CTIS Part Ii Submission Date

20-11-2024

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

380

Number Of Sites

9

Number Of Participants

38

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy