SIERRA: Durvalumab and Tremelimumab as First Line Treatment in Participants with Advanced Hepatocellular Carcinoma

Phase 1

Recruiting

• Conditions: Advanced Hepatocellular Carcinoma; MedDRA version: 20.0Level: PTClassification code: 10073071Term: Hepatocellular carcinoma Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-502012-37-00
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-11
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

1. Participant must be = 18 years at the time of screening., 12. Body weight of > 30 kg., 13. Male or female., 9. Participants with HBV infection (as characterized by positive HbsAg and/or anti-HbcAb with detectable HBV DNA, as per local laboratory standards) must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (as per local laboratory standards) prior to enrolment. Participants must remain on antiviral therapy for the study duration and for 6 months after the last dose of study intervention. Participants who test positive for anti-HBc with undetectable HBV DNA (as per local laboratory standards) do not require antiviral therapy prior to enrolment. These participants will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (as per local laboratory standards). HBV DNA detectable participants must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study intervention., 11. 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) Haemoglobin = 9.0 g/dL (b) Absolute neutrophil count = 1000/µL (c) Platelet count = 75000/µL (d) TBL = 2.5 × the ULN or = 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia)* (e) ALT and AST = 5 × ULN* (f) Albumin = 2.6 g/dL* (g) INR < 2.3 (h) Calculated creatinine clearance > 40 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance. *Accurate baseline AST, ALT, TBL, and albumin levels must be determined by having 2 measurements 5 days apart during screening, with less than 33% for decompensated liver cirrhosis, or 40% for compensated cirrhosis, variability between them before enrolment. Higher variability should lead to a further test to determine whether there is significant or rapid decompensation that could affect study participation. The baseline values for AST, ALT, TBL, and albumin will be the mean of the 2 values obtained during screening., 10. Participants with HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV RNA or anti-HCV upon enrolment (management of this disease is per local institutional practice)., 2. Confirmed HCC based on histopathological findings from tumour tissue., 16. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening throughout the total duration of the study and the drug washout period (180 days after the last dose of durvalumab and tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. (a) Female partners (of childbearing potential) of male participants must also use a highly effective method of contraception throughout this period., 17. Capable of giving signed informed consent., 18. Written informed consent from the participant has been obtained prior to any study-related procedures., 3. Must not have received prior systemic therapy for HCC., 4. Minimum life expectancy of 12 weeks., 5. At least 1 measurable lesion, not previously irradiated, th

Exclusion Criteria

1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active COVID-19, uncontrolled hypertension, active bleeding diseases, active infection, active interstitial lung disease/pneumonitis, serious chronic GI conditions associated with diarrhoea, psychiatric illness/social situations) or history of allogeneic organ transplant (eg, liver transplant) or those eligible to receive a transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol., 25. Participation in another clinical study with a study intervention or investigational medicinal device administered within 28 days prior to first dose of study intervention or concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study., 26. Participants with a known allergy or hypersensitivity to durvalumab and/or tremelimumab or any of the excipients of the product., 15. Participants co-infected with HBV (presence of HbsAg and/or anti-HbcAb with detectable HBV DNA, as per local laboratory standards) and HCV (presence of anti-HCV antibodies), or co-infected with HBV and HDV (presence of anti-HDV antibodies)., 19. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants, if enrolled, should not receive live vaccine while receiving study intervention and up to 30 days after the last dose., 10. Clinically meaningful ascites, defined as ascites requiring escalation in pharmacologic intervention and/or increasingly frequent paracentesis to maintain symptomatic control within 2 months prior to the first scheduled dose. Participants on stable doses of diuretics for ascites or requiring occasional paracentesis for = 2 months are eligible. Also uncontrolled pleural effusion, pericardial effusion requiring recurrent drainage procedures (once monthly or more frequently)., 20. Receipt of the last dose of anticancer therapy (tumour embolisation) 28 days prior to the first dose of study intervention or 5 half-lives of the respective study intervention, whichever is longer., 11. Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within the past 6 months. Note: For participants with a history of GI bleeding greater than 6 months or assessed as high risk for esophageal varices by the investigator, including main trunk portal vein thrombosis, a recent endoscopy within 3 months of enrolment and adequate endoscopic therapy according to institutional standards is required., 2. Refractory nausea and vomiting, chronic GI disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of medication(s) needed to control participant’s symptoms., 3. History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted., 4. Hi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified