Sequential or up-front triple treatment with durvalumab, tremelimumab and bevacizumab for non-resectable hepatocellular carcinoma (HCC) patients (MONTBLANC)
- Conditions
- non-resectable hepatocellular carcinoma (HCC)MedDRA version: 21.0Level: LLTClassification code: 10019828Term: Hepatocellular carcinoma non-resectable Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-511439-84-00
- Lead Sponsor
- Klinikum der Universitaet Muenchen AöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 83
1.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 (European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations., 10.Patients with HBV infection, characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (=10 IU/ml or above the limit of detection per local or central lab standard), must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (HBV DNA =2000 IU/mL) prior to enrollment. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local or central lab standard) do not require anti-viral therapy prior to enrollment. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (=10 IU/ml or above the limit of detection per local or central lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication., 11.Patients with HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV RNA or anti-HCV antibody upon enrollment (management of this disease is per local institutional practice)., 12.At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes, which must have a short axis =15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria., 13.Adequate organ and marrow function, as defined below. Criteria a,” b,” c,” and f” cannot be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose. a.Hemoglobin =9 g/dL b.Absolute neutrophil count =1500/µL c.Platelet count =75000/µL d.Total bilirubin (TBL) =2.0× upper limit of normal (ULN) e.AST and ALT =5×ULN f.Albumin =2.8 g/dL g.International normalized ratio (INR) =1.6. Note: INR prolongation due to anticoagulants for prophylaxis (e.g., atrial fibrillation) in patients without liver cirrhosis could be exception. h.Calculated creatinine clearance =50 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance i.Urine dipstick for proteinuria < 2+ (within 7 days prior to initiation of study treatment), unless a subsequent 24-hour urine collection demonstrates < 1 g of protein in 24 hours., 14.Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients., 15.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up., 16.Must have a life expectancy of at least 12 weeks., 2.Age =18 years at the tim
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)., History of allogeneic organ transplantation (eg, liver transplant)., History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy)., Clinically meaningful ascites, defined as any ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Subjects on stable doses of diuretics for ascites for =2 months are eligible., Patients with main portal vein thrombosis (i.e., thrombosis in the main trunk of the portal vein, with or without blood flow) on baseline imaging., Patient currently exhibits symptomatic or uncontrolled hypertension defined as diastolic blood pressure >90 mmHg or systolic blood pressure >140 mmHg., Any condition interfering with swallowing pills, uncontrolled diarrhea, or other contraindication to oral therapy., Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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, etc]). Patients without active disease in the last 5 years are excluded unless discussed with the Study Physician and considered appropriate for study participation. The following are exceptions to this criterion: a) Patients with vitiligo or alopecia b) Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement c) Any chronic skin condition that does not require systemic therapy d) Patients with celiac disease controlled by diet alone., Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). HBV positive (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA); HCV positive (presence of anti-HCV antibodies); HDV positive (presence of anti- HDV antibodies)., Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhea, inferior vena cava thrombosis, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent., 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 study drug(s) and of low potential risk for recurrence b) Patients with a history of prostate cancer of stage =T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention. c) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease d) Adequately treated carcinoma in situ without evidence of disease., Previous study drug(s) assignment in the present study., History of leptomeningeal carcinomatosis., History of, or current, brain metastases or spinal cord compression. Patients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method