Himalaya Early Access Program

NCT05345678 | Unknown

• 1 other identifier: D419CR00019
• Study Type: expanded_access
• Target: N/A
• Locations: 1 country
• Sites: 4

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.

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

Unresectable Hepatocellular Carcinoma

Interventions

Durvalumab DRUG

Dose: 1500mg Route: IV

Also known as: Imfinzi

Tremelimumab DRUG

Dose: 300mg Route: IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and over at the time of screening.
• Body weight over 30 kg.
• Confirmed HCC based on histopathological findings from tumour tissues.
• Must not have received prior systemic therapy for HCC.
• 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.
• Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C (refer to Appendix H).
• Child-Pugh Score Class A; or Child-Pugh Class B7 or B8 at discretion of treating physician (refer to Appendix I).
• 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.
• 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).
• 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.
• 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.
• Haemoglobin ≥9 g/dL
• Absolute neutrophil count ≥1000/μL
• Platelet count ≥75,000/μL
• Total bilirubin (TBL) ≤2.0 x upper limit of normal (ULN)

You may not qualify if:

• Concurrent enrolment in a clinical study unless it is an observational (non interventional) clinical study or during the follow-up period of an interventional study.
• Have received an investigational product within 28 days before the first dose of EAP treatment.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Treating Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Treating Physician.
• Any concurrent chemotherapy, study drug, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Known allergy or hypersensitivity to any of the EAP treatments or any of the EAP treatment excipients.
• Child-Pugh Score Class B9; or Child-Pugh Class C
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of EAP treatments.
• Major surgical procedure (as defined by the Treating Physician) within 28 days before the first dose of EAP treatment. Note: local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation (e.g., liver transplant).
• History of hepatic encephalopathy within the past 12 months or requirement for medications to prevent or control encephalopathy (e.g., no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy.
• Clinically meaningful ascites, defined as any ascites requiring non-pharmacologic intervention (e.g., paracentesis) to maintain symptomatic control, within 6 months before the first EAP treatment dose. Patients 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.
• Active or previously documented GI bleeding (e.g., oesophageal varices or ulcer bleeding) within 12 months. (Note: for patients with history of GI bleeding for \>12 months or assessed as high risk for oesophageal variceal by the Treating Physician, adequate endoscopic therapy according to institutional standards is required).
• Patient currently exhibits symptomatic or uncontrolled hypertension defined as diastolic blood pressure \>90 mmHg or systolic blood pressure \>140 mmHg.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Newark, Delaware, 19718, United States

Location

Research Site

Minneapolis, Minnesota, 55404, United States

Location

Research Site

Reno, Nevada, 89502, United States

Location

Research Site

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Interventions

durvalumab; tremelimumab

Study Design

• Study Type: expanded access
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: April 26, 2022
• Last Updated: December 14, 2022

Record last verified: 2022-12

Locations

US (4)