Unresectable Hepatocellular Carcinoma
Conditions
Keywords
Unresectable Hepatocellular Carcinoma
Brief summary
To provide early access (i.e., before marketing authorisation) to tremelimumab 300 mg IV administered once on Day 1 of Cycle 1 plus durvalumab 1500 mg IV followed by durvalumab 1500 mg IV Q4W monotherapy in patients with unresectable HCC.
Detailed description
Overall design This is a multi centre, open-label, early access program (EAP) designed to provide treatment access to intravenous (IV) combination treatment regimen of 300 mg tremelimumab administered IV once on Day 1 of Cycle 1 plus 1500 mg durvalumab IV (MEDI 4736) followed by durvalumab IV monotherapy administered once every 4 weeks (Q4W) for eligible patients with unresectable, hepatocellular carcinoma (HCC). Durvalumab and tremelimumab will be provided free of charge to the patients entering this program. This global EAP will be opened in a staggered fashion, country by country, based on the requesting Treating Physician(s) and local regulations, ending when durvalumab and tremelimumab has received marketing authorisation in first line treatment in patients with unresectable hepatocellular carcinoma. Target patient population Patients with unresectable HCC and Barcelona Clinic Liver Cancer (BCLC) stage B (who are not eligible or no longer suitable for locoregional therapy \[LRT\]) or stage C before entering the EAP. Program period The EAP will enrol patients and provide resupply of durvalumab and tremelimumab until durvalumab and tremelimumab has received marketing authorisation in first line treatment for patients with unresectable HCC as per local regulations. The EAP will be closed to new patients based on local regulations or when commercially reimbursed product is available. After reimbursement is secured, or denial of reimbursement, or decision by the Sponsor to close the enrolment, whichever occurs first, no new patients can be enrolled after this point. In the event that market license approval or reimbursement should not be granted, contingencies will be made to ensure continued drug supply for patients who are still deriving benefit from durvalumab and tremelimumab. Number of patients: The number of patients who will enrol in the EAP is based on approval of unsolicited requests received from the Treating Physician. Program treatment: On Day 1 of Cycle 1, tremelimumab will be administered first followed by durvalumab 1 hour later. Tremelimumab will be given once on Day 1 of Cycle 1. Durvalumab monotherapy is then given Q4W. Duration of treatment: Patients may continue to receive EAP treatment providing they continue to show clinical benefit, as judged by the Treating Physician, in the absence of unacceptable safety concerns until disease progression, toxicity or withdrawal.
Interventions
DRUGDurvalumab
Dose: 1500mg Route: IV
DRUGTremelimumab
Dose: 300mg Route: IV
Sponsors
AstraZeneca
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years and over at the time of screening. 2. Body weight over 30 kg. 3. Confirmed HCC based on histopathological findings from tumour tissues. 4. Must not have received prior systemic therapy for HCC. 5. Must not be eligible for locoregional therapy for resectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed at least 28 days before the baseline scan for the programme. 6. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C (refer to Appendix H). 7. Child-Pugh Score Class A; or Child-Pugh Class B7 or B8 at discretion of treating physician (refer to Appendix I). 8. Patients with HBV infection, characterised by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV deoxyribonucleic acid (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) before enrolment. Patients must remain on antiviral therapy for the duration of their participation in the EAP and for 6 months after the last dose of EAP 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 before enrolment. These participants will be tested at every cycle to monitor HBV DNA levels and initiate anti-viral therapy if HBV DNA is detected (≥10 IU/mL or above the limit of detection per local or central lab standard). HBV DNA detectable patients must initiate and remain on anti-viral therapy for time they are in the EAP and for 6 months after the last dose of EAP medication. 9. Patients with HCV infection must have confirmed diagnosis of HCV characterised by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrolment (management of this disease is per local institutional practice). 10. At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline ≥10 mm in the longest diameter (except lymph nodes, which must have as short axis ≥15 mm) with computerised tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines (Eisenhauer et al, 2009). A lesion which progressed after previous ablation or transarterial chemoembolization (TACE) could be measurable if it meets these criteria. 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 of EAP treatment. 1. Haemoglobin ≥9 g/dL 2. Absolute neutrophil count ≥1000/μL 3. Platelet count ≥75,000/μL 4. Total bilirubin (TBL) ≤2.0 x upper limit of normal (ULN) 5. AST and ALT ≤5xULN 6. Albumin ≥2.8 g/dL 7. International normalised ratio (INR) ≤1.6. Note: INR prolongation due to anticoagulants for prophylaxis (e.g., atrial fibrillation) in patients without liver cirrhosis could be exception. 8. Calculated creatinine clearance ≥50 mL/minute as determined by Cockcroft Gault (using actual body weight) or 24-hour urine creatinine clearance 12. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal as described in Section 5.3.4. 13. Must have a life expectancy of at least 12 weeks. 14. Willing and able to comply with the protocol for the duration of the EAP including undergoing treatment and scheduled visits and examination including follow up. 15. Able to provide written informed consent and any locally-required authorisation (e.g., Health Insurance Portability and Accountability Act \[HIPAA\] in the United States \[US\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative before performing any protocol-related procedures, including screening evaluations.
Exclusion criteria
Patients should not enter the EAP if any of the following
Countries
United States
Outcome results
None listed